Methods and apparatuses for determining contact lens intolerance in contact lens wearer patients based on dry eye tear film characteristic analysis and dry eye symptoms

ABSTRACT

Methods and apparatuses for determining contact lens intolerance in contact lens wearer patients based on tear film characteristics analysis and dry eye symptoms are disclosed. In embodiments herein, imaging of the ocular tear film is performed during contact lens wear. An analysis of the image of the ocular tear film is performed to determine one or more tear film characteristics of the ocular tear film. The tear film characteristics can be used to determine the effect or possible effect of contact lens wear on the ocular tear film, and thus be used to determine contact lens intolerance of the patient. The tear film characteristics used to analyze contact lens intolerance based on images of the ocular tear film involving contact lens wear may include dry eye symptoms, including but not limited to tear film (e.g., lipid and/or aqueous) thickness, tear film viscosity, and tear film movement rate in the eye.

PRIORITY APPLICATION

The present application claims priority to U.S. Provisional PatentApplication Ser. No. 61/819,125 entitled “APPARATUSES AND METHODS FORDETERMINING CONTACT LENS INTOLERANCE AND DIAGNOSING, MEASURING, AND/ORANALYZING DRY EYE CONDITIONS AND SYMPTOMS IN CONTACT LENS WEARERS,”filed on May 3, 2013, which is incorporated herein by reference in itsentirety.

The present application claims priority to U.S. Provisional PatentApplication Ser. No. 61/904,562 entitled “OCULAR SURFACE INTERFEROMETRY(OSI) SYSTEM AND METHODS FOR IMAGING, PROCESSING, AND/OR DISPLAYING ANOCULAR TEAR FILM AND MEIBOMIAN GLAND FEATURES,” filed on Nov. 15, 2013,which is incorporated herein by reference in its entirety.

The present application is a continuation in part of U.S. patentapplication Ser. No. 12/798,275 entitled “OCULAR SURFACE INTERFEROMETRY(OSI) DEVICES AND SYSTEMS FOR IMAGING, PROCESSING, AND/OR DISPLAYING ANOCULAR TEAR FILM,” filed on Apr. 1, 2010, which claims priority to U.S.Provisional Patent Application Ser. No. 60/211,596 entitled “OCULARSURFACE INTERFEROMETRY (OSI) METHODS FOR IMAGING PROCESSING, AND/ORDISPLAYING AN OCULAR TEAR FILM,” filed on Apr. 1, 2009, which are bothincorporated herein by reference in their entireties.

RELATED APPLICATIONS

The present application is related to U.S. patent application Ser. No.12/798,325 entitled “OCULAR SURFACE INTERFEROMETRY (OSI) METHODS FORIMAGING, PROCESSING, AND/OR DISPLAYING AN OCULAR TEAR FILM,” filed onApr. 1, 2010, issued as U.S. Pat. No. 8,545,017, which claims priorityto U.S. Provisional Patent Application Ser. No. 60/211,596 entitled“OCULAR SURFACE INTERFEROMETRY (OSI) METHODS FOR IMAGING, PROCESSING,AND/OR DISPLAYING AN OCULAR TEAR FILM,” filed on Apr. 1, 2009, which areboth incorporated herein by reference in their entireties.

The present application is also related to U.S. patent application Ser.No. 12/798,326 entitled “OCULAR SURFACE INTERFEROMETRY (OSI) METHODS FORIMAGING AND MEASURING OCULAR TEAR FILM LAYER THICKNESS(ES),” filed onApr. 1, 2010, issued as U.S. Pat. No. 8,092,023, which claims priorityto U.S. Provisional Patent Application Ser. No. 60/211,596 entitled“OCULAR SURFACE INTERFEROMETRY (OSI) METHODS FOR IMAGING, PROCESSING,AND/OR DISPLAYING AN OCULAR TEAR FILM,” filed on Apr. 1, 2009, which areboth incorporated herein by reference in their entireties.

The present application is also related to U.S. patent application Ser.No. 12/798,324 entitled “OCULAR SURFACE INTERFEROMETRY (OSI) DEVICES ANDSYSTEMS FOR IMAGING AND MEASURING OCULAR TEAR FILM LAYER THICKNESS(ES),”filed on Apr. 1, 2010, issued as U.S. Pat. No. 8,215,774, which claimspriority to U.S. Provisional Patent Application Ser. No. 60/211,596entitled “OCULAR SURFACE INTERFEROMETRY (OSI) METHODS FOR IMAGING,PROCESSING, AND/OR DISPLAYING AN OCULAR TEAR FILM,” filed on Apr. 1,2009, which are both incorporated herein by reference in theirentireties.

The present application is also related to co-pending U.S. patentapplication Ser. No. 13/886,383 entitled “OPTICAL PHANTOMS FOR USE WITHOCULAR SURFACE INTERFEROMETRY (OSI) DEVICES AND SYSTEMS CONFIGURED TOMEASURE TEAR FILM LAYER THICKNESS(ES), AND RELATED USE FOR CALIBRATION,”filed on May 3, 2013, which claims priority to U.S. Provisional PatentApplication Ser. No. 61/642,688, entitled “OPTICAL PHANTOMS FOR USE WITHOCULAR SURFACE INTERFEROMETRY (OSI) DEVICES AND SYSTEMS CONFIGURED TOMEASURE TEAR FILM LAYER THICKNESS(ES), AND RELATED USE FOR CALIBRATION,”filed on May 4, 2012, which are both incorporated herein by reference intheir entireties.

The present application is being filed with color versions (3 sets) ofthe drawings discussed and referenced in this disclosure. Color drawingsmore fully disclose the subject matter disclosed herein.

FIELD OF THE DISCLOSURE

The technology of the disclosure relates to imaging and analysis of apatient's ocular tear film to determine tear film characteristicsrelating to dry eye symptoms, including lipid layer deficiency, incontact lens wearers.

BACKGROUND

In the human eye, the precorneal tear film covering ocular surfaces iscomposed of three primary layers: the mucin layer, the aqueous layer,and the lipid layer. Each layer plays a role in the protection andlubrication of the eye and thus affects dryness of the eye or lackthereof. Dryness of the eye is a recognized ocular disease, which isgenerally referred to as “dry eye,” “dry eye syndrome” (DES), or“keratoconjunctivitis sicca” (KCS). Dry eye can cause symptoms, such asitchiness, burning, and irritation, which can result in discomfort.There is a correlation between the ocular tear film layer thicknessesand dry eye disease. The various different medical conditions and damageto the eye as well as the relationship of the aqueous and lipid layersto those conditions are reviewed in Surv Opthalmol 52:369-374, 2007 andadditionally briefly discussed below.

As illustrated in FIG. 1, the precorneal tear film includes an innermostlayer of the tear film in contact with a cornea 10 of an eye 11 known asthe mucus layer 12. The mucus layer 12 is comprised of many mucins. Themucins serve to retain aqueous in the middle layer of the tear filmknown as the aqueous layer. Thus, the mucus layer 12 is important inthat it assists in the retention of aqueous on the cornea 10 to providea protective layer and lubrication, which prevents dryness of the eye11.

A middle or aqueous layer 14 comprises the bulk of the tear film. Theaqueous layer 14 is formed by secretion of aqueous by lacrimal glands 16and accessory tear glands 17 surrounding the eye 11, as illustrated inFIG. 2A. FIG. 2B illustrates the eye 11 in FIG. 2A during a blink. Theaqueous, secreted by the lacrimal glands 16 and accessory tear glands17, is also commonly referred to as “tears.” One function of the aqueouslayer 14 is to help flush out any dust, debris, or foreign objects thatmay get into the eye 11. Another important function of the aqueous layer14 is to provide a protective layer and lubrication to the eye 11 tokeep it moist and comfortable. Defects that cause a lack of sufficientaqueous in the aqueous layer 14, also known as “aqueous deficiency,” area common cause of dry eye.

The outermost layer of the tear film, known as the “lipid layer” 18 andalso illustrated in FIG. 1, also aids to prevent dryness of the eye. Thelipid layer 18 is comprised of many lipids known as “meibum” or “sebum”that is produced by meibomian glands 20 in upper and lower eyelids 22,24, as illustrated in FIG. 3. This outermost lipid layer is very thin,typically less than 250 nanometers (nm) in thickness. The lipid layer 18provides a protective coating over the aqueous layer 14 to limit therate at which the aqueous layer 14 evaporates. Blinking causes the uppereyelid 22 to mall up aqueous and lipids as a tear film, thus forming aprotective coating over the eye 11. A higher rate of evaporation of theaqueous layer 14 can cause dryness of the eye. Thus, if the lipid layer18 is not sufficient to limit the rate of evaporation of the aqueouslayer 14, dryness of the eye may result.

For wearers of contact lenses, a widely reported ailment to physiciansis intolerance to prolonged contact lens usage. Contact lens wear cancontribute to dry eye. A contact lens can disrupt the natural tear filmand can reduce corneal sensitivity over time, which can cause areduction in tear production. In some patients, contact lens wearbecomes unmanageable due to pain, irritation, or general decrease ofvisual acuity due to ocular discomfort. Typical remedies includerepetitive eye drop applications, alterations of daily activity, orrepeated removal of the contact lenses and return to standard eyeglassesor poor vision. For physicians, a typical treatment regime of revisedmedications and replacement contact lenses is tried and evaluated untila recommendation to alternative vision correction is employed for thepatient. For many of these patients, evaporative dry eye disease is anunderlying cause for their contact lens intolerance.

A system for determining which patients would be ideal candidates, ornon-candidates for contact lenses, in the presence of ongoing dry eyedisease would be of benefit to physicians and patients. Since dry eyedisease can be an underlying problem as in the case of meibomian glanddysfunction (MGD) or non-obvious meibomian gland disease, a system thatcan be predictive of future contact lens problems would be advantageous.For MGD or meibomian gland disease in which dry eye signs are visible tothe physician, a system that can qualitatively assess the potentialimpact of contact lens wear to the patient prospectively would be abenefit to future contact lens wear and the selection of model type.

SUMMARY

Methods and apparatuses for determining contact lens intolerance incontact lens wearer patients based on tear film characteristics analysisand dry eye symptoms are disclosed. An ocular tear film may be affectedby contact lens wear. Contact lens wear can contribute to dry eye. Acontact lens can disrupt the natural tear film and can reduce cornealsensitivity over time, which can cause a reduction in tear filmproduction. For many patients, evaporative dry eye disease is anunderlying cause for their contact lens intolerance. Thus, inembodiments herein, imaging of the ocular tear film is performed duringcontact lens wear or at time points immediately preceding or followingcontact lens wear. For example, the imaging may include captured opticalwave interference of specularly reflected light from the ocular tearfilm, when the ocular tear film is illuminated with the light source. Ananalysis of the image of the ocular tear film is performed to determineone or more tear film characteristics of the ocular tear film. The tearfilm characteristics can be used to determine the effect or possibleeffect of contact lens wear on the ocular tear film, and thus be used todetermine contact lens intolerance of the patient. As examples, the tearfilm characteristics used to analyze contact lens intolerance based onimages of the ocular tear film involving contact lens wear may includedry eye symptoms, including but not limited to tear film thickness, tearfilm viscosity, and tear film movement rate in the eye. When referringto tear film herein, it should be noted that such refers to the lipidlayer and/or the aqueous layer of the ocular tear film.

In this regard, in one embodiment, a method for diagnosing contact lensintolerance on an ocular tear film of a patient is provided. The methodcomprises illuminating the ocular tear film of the patient with acontact lens disposed on a patient's eye with a light source. The methodalso comprises capturing in at least one first image of the ocular tearfilm without the contact lens disposed on the patient's eye, opticalwave interference of specularly reflected light from the ocular tearfilm, when the ocular tear film is illuminated with the light source.The method also comprises isolating at least one contact lens-basedregion of interest in the at least one first image where the contactlens is present on the ocular tear film. The method also comprisesconverting the at least one contact lens-based region of interest in theat least one first image into at least one contact lens-basedcolor-based value. The method also comprises comparing the at least onecontact lens-based color-based value to a lipid layer-contact lens layeroptical wave interference model. The method also comprises determining acontact lens-based tear film characteristic of the at least one contactlens-based region of interest of the ocular tear film based on thecomparison of the at least one contact lens-based color-based value tothe lipid layer-contact lens layer optical wave interference model.

In another embodiment, an apparatus for diagnosing contact lensintolerance on an ocular tear film of a patient is provided. Theapparatus comprises a light source configured to illuminate the oculartear film of a patient without a contact lens disposed on a patient'seye. The apparatus also comprises an imaging device configured tocapture in at least one first image of the ocular tear film without thecontact lens disposed on the patient's eye, optical wave interference ofspecularly reflected light from the ocular tear film, when the oculartear film is illuminated with the light source. The apparatus alsocomprises a computer control system. The computer control system isconfigured to isolate at least one contact lens-based region of interestin the at least one first image where the contact lens is present on theocular tear film. The computer control system is also configured toconvert the at least one contact lens-based region of interest in the atleast one first image into at least one contact lens-based color-basedvalue. The computer control system is also configured to compare the atleast one contact lens-based color-based value to a lipid layer-contactlens layer optical wave interference model. The computer control systemis also configured to determine a contact lens-based tear filmcharacteristic of the at least one contact lens-based region of interestof the ocular tear film based on the comparison of the at least onecontact lens-based color-based value to the lipid layer-contact lenslayer optical wave interference model.

In another embodiment, a method for diagnosing contact lens intolerancein a patient is provided. The method comprises illuminating an oculartear film of a patient having a contact lens disposed on a patient'seye. The method also comprises capturing in at least one first image ofthe ocular tear film with the contact lens disposed on the patient'seye, optical wave interference of specularly reflected light from theocular tear film, when the ocular tear film is illuminated. The methodalso comprises isolating at least one non-contact lens-based region ofinterest in the at least one first image where the contact lens is notpresent on the ocular tear film. The method also comprises determining anon-contact lens-based tear film characteristic in the at least onenon-contact lens-based region of interest of the at least one firstimage.

In another embodiment, an apparatus for diagnosing contact lensintolerance in a patient is provided. The apparatus comprises anilluminator configured to illuminate an ocular tear film of a patienthaving a contact lens disposed on a patient's eye. The apparatus alsocomprises an imaging device configured to capture in at least one firstimage of the ocular tear film with the contact lens disposed on thepatient's eye, optical wave interference of specularly reflected lightfrom the ocular tear film, when the ocular tear film is illuminated. Theapparatus also comprises a computer control system. The computer controlsystem is configured to isolate at least one non-contact lens-basedregion of interest in the at least one first image where the contactlens is not present on the ocular tear film. The computer control systemis also configured to determine a non-contact lens-based tear filmcharacteristic in the at least one non-contact lens-based region ofinterest of the at least one first image.

Those skilled in the art will appreciate the scope of the presentdisclosure and realize additional aspects thereof after reading thefollowing detailed description of the preferred embodiments inassociation with the accompanying drawing figures.

BRIEF DESCRIPTION OF FIGURES

The patent or application file contains at least one drawing executed incolor. Copies of this patent or patent application publication withcolor drawing(s) will be provided by the Office upon request and paymentof the necessary fee.

FIG. 1 is a side view of an exemplary eye showing the three layers ofthe tear film in exaggerated form;

FIG. 2A is a front view of an exemplary eye showing the lacrimal andaccessory tear glands that produce aqueous in the eye;

FIG. 2B is a front view of an exemplary eye in FIG. 2A during a blink;

FIG. 3 illustrates exemplary upper and lower eyelids showing themeibomian glands contained therein;

FIGS. 4A and 4B are illustrations of an exemplary light source andimaging device to facilitate discussion of illumination of the tear filmand capture of interference interactions of specularly reflected lightfrom the tear film;

FIG. 5 illustrates (in a microscopic section view) exemplary tear filmlayers to illustrate how light rays can specularly reflect from varioustear film layer transitions;

FIG. 6 is a flowchart of an exemplary process for determining tear filmcharacteristics of a patient's ocular tear film based on analysis ofimaged optical wave interference of specularly reflected light from acontact lens-based region of interest of the patient's tear film duringcontact lens wear, to determine the patient's intolerance to contactlens wear;

FIG. 7 illustrates a first image focused on a lipid layer of a patient'stear film while the patient is wearing a contact lens, and capturinginterference interactions of specularly reflected light from an area orregion of interest of the tear film;

FIG. 8 illustrates a second image focused on the lipid layer of the tearfilm in FIG. 7 and capturing background signal when not illuminated bythe light source;

FIG. 9 illustrates an image of the tear film when background signalcaptured in the second image of FIG. 8 is subtracted from the firstimage of FIG. 7;

FIG. 10 illustrates the image of the tear film in FIG. 9 with a contactlens-based region of interest in the image isolated to determine andanalyze one or more tear film characteristics of the contact lens-basedregion of interest of the tear film and/or analyze one or more tear filmcharacteristics of a non-contact lens-based region of interest of thetear film to determine the effect of contact lens wear on the patient'stear film;

FIG. 11 illustrates a first image focused on the lipid layer of the tearfilm capturing interference interactions of specularly reflected lightand background signal from tiled portions in an area or region ofinterest of the tear film during contact lens wear;

FIG. 12 illustrates a second image focused on the lipid layer of thetear film in FIG. 11 capturing background signal and interferenceinteractions of specularly reflected light from the tiled portions inthe area or region of interest in FIG. 11, respectively during contactlens wear;

FIG. 13 illustrates an image when the background signal captured indiffusely illuminated tiled portions in the first and second images ofFIGS. 11 and 12 are subtracted or substantially subtracted from thespecularly reflected light in corresponding tiled portions in the firstand second images of FIGS. 11 and 12;

FIG. 14 is a perspective view of an exemplary ocular surfaceinterferometry (OSI) device for illuminating and imaging a patient'stear film involving contact lens wear, displaying images, analyzing tearfilm characteristics of the tear film, and generating results from theanalysis of the patient's tear film;

FIG. 15 is a side view of the OSI device of FIG. 14 illuminating andimaging a patient's eye and tear film;

FIG. 16 is a side view of a video camera and illuminator within the OSIdevice of FIG. 14 imaging a patient's eye and tear film;

FIG. 17 illustrates an exemplary system diagram of a control system andsupporting components in the OSI device of FIG. 14 that allow imaging apatient's tear film during contact lens wear to determine tear filmcharacteristics of the tear film for determining contact lensintolerance of the patient;

FIG. 18 is a flowchart illustrating an exemplary overall processing flowof the OSI device of FIG. 14 having systems components according to theexemplary system diagram of the OSI device in FIG. 17;

FIG. 19 is a flowchart illustrating exemplary pre-processing stepsperformed on the combined first and second images of a patient's tearfilm involving contact lens wear before measuring tear film layerthickness (TFLT);

FIG. 20 is an exemplary graphical user interface (GUI) for controllingimaging, pre-processing, and post-processing settings of the OSI deviceof FIG. 14;

FIG. 21 illustrates an example of a subtracted image in an area orregion of interest of a tear film involving contact lens wear thatcontains specularly reflected light from the tear film overlaid on topof a background image of the tear film;

FIGS. 22A and 22B illustrate exemplary threshold masks that may be usedto provide a threshold function during pre-processing of a resultingimage containing specularly reflected light from a patient's tear filminvolving contact lens wear;

FIG. 23 illustrates an exemplary image of FIG. 21 after a thresholdpre-processing function has been performed leaving interference of thespecularly reflected light from the patient's tear film involvingcontact lens wear;

FIG. 24 illustrates an exemplary image of the image of FIG. 23 aftererode and dilate pre-processing functions have been performed on theimage;

FIG. 25 illustrates an exemplary process for loading an InternationalColour Consortium (ICC) profile and tear film interference model intothe OSI device of FIG. 14;

FIG. 26 illustrates a flowchart providing an exemplary visualizationsystem process for displaying images of a patient's tear film involvingcontact lens wear on a display in the OSI device of FIG. 14;

FIGS. 27A-27C illustrate exemplary images of a patient's tear filminvolving contact lens wear with a tiled pattern of interferenceinteractions from specularly reflected light from the tear filmdisplayed on a display;

FIG. 28 illustrates an exemplary post-processing system that may beprovided in the OSI device of FIG. 14;

FIG. 29A illustrates an exemplary 3-wave tear film interference modelbased on a 3-wave theoretical tear film model to correlate differentobserved interference color with different lipid layer thicknesses(LLTs) and aqueous layer thicknesses (ALTs);

FIG. 29B illustrates another exemplary 3-wave tear film interferencemodel based on a 3-wave theoretical tear film model to correlatedifferent observed interference color with different lipid layerthicknesses (LLTs) and aqueous layer thicknesses (ALTs);

FIG. 30 is another representation of the 3-wave tear film interferencemodel of FIG. 27A and/or FIG. 27B with normalization applied to eachred-green-blue (RGB) color value individually;

FIG. 31 is an exemplary histogram illustrating results of a comparisonof interference interactions from the interference signal of specularlyreflected light from a patient's tear film involving contact lens wearto the 3-wave tear film interference model of FIGS. 29A, 29B, and 30 formeasuring TFLT of a patient's tear film involving contact lens wear as atear film characteristic;

FIG. 32 is an exemplary histogram plot of distances in pixels betweenRGB color value representation of interference interactions from theinterference signal of specularly reflected light from a patient's tearfilm involving contact lens wear and the nearest distance RGB colorvalue in the 3-wave tear film interference model of FIGS. 29A, 29B, and30;

FIG. 33 is an exemplary threshold mask used during pre-processing of thetear film images involving contact lens wear;

FIG. 34 is an exemplary three-dimensional (3D) surface plot of themeasured LLT and ALT thicknesses of a patient's tear film involvingcontact lens wear;

FIG. 35 is an exemplary image representing interference interactions ofspecularly reflected light from a patient's tear film involving contactlens wear results window based on replacing a pixel in the tear filmimage with the closest matching RGB color value in the normalized 3-wavetear film interference model of FIG. 30;

FIG. 36 is an exemplary TFLT palette curve for a TFLT palette of LLTsplotted in RGB space for a given ALT in three-dimensional (3D) space;

FIG. 37 is an exemplary TFLT palette curve for the TFLT palette of FIG.36 with LLTs limited to a maximum LLT of 240 nm plotted in RGB space fora given ALT in three-dimensional (3D) space;

FIG. 38 illustrates the TFLT palette curve of FIG. 37 with an acceptabledistance to palette (ADP) filter shown to determine tear film pixelvalues having RGB values that correspond to ambiguous LLTs;

FIG. 39 is an exemplary graph that can be displayed on the display ofthe OSI device in FIG. 14 representing a patient's tear film movementstabilization during contact lens wear following eye blinks;

FIG. 40 is a flowchart illustrating an exemplary process for determininga patient's tear film movement during contact lens wear following eyeblinks indicative of a patient's tear film thickness stabilizationfollowing eye blink during contact lens wear;

FIG. 41 is an exemplary velocity vector image representing interferenceinteractions of specularly reflected light from a contact lens wearerpatient's tear film;

FIG. 42 is a close up side view of a patient's cornea during contactlens wear and a tear film disposed on top of the patient's contact lens,and determining tear film characteristics of the patient's tear film asthe slope of the meniscus;

FIG. 43 is a flowchart of an exemplary process for determining tear filmcharacteristics of a patient's ocular tear film based on analysis ofimaged optical wave interference of specularly reflected light from anon-contact lens-based region of interest of the patient's tear filmduring contact lens wear, to determine the patient's intolerance tocontact lens wear;

FIG. 44 is a block diagram of the OSI device configured to calibrate theOSI device to make accurate tear film measurements;

FIG. 45 is a flowchart of an exemplary procedure for calibrating the OSIdevice to make tear film measurements;

FIG. 46 is an exemplary RGB plot of an exemplary theoretical lipid colorpalette with points selected for optical phantoms;

FIG. 47 is a table of lipid layer thicknesses of the selected pointsshown in FIG. 46 along with their corresponding optical path lengths andphantom thicknesses;

FIG. 48 is a diagram that illustrates exemplary wedge phantomellipsometry measurement points;

FIG. 49 is a table listing exemplary phantom lipid layer thicknesses fornine exemplary sample phantom wedges measured using exemplaryellipsometry along with corresponding biological lipid layerthicknesses;

FIG. 50 is a table that presents a comparison of expected exemplaryinterference colors from optical phantoms and a theoretical model;

FIG. 51 is a graph that compares an original exemplary lipid colorpalette with a new exemplary lipid color palette based on the phantommeasurements;

FIG. 52 is a flowchart of an exemplary process for determining alipid-layer-contact lens layer optical wave interference model based oncalibrating a tear film optical wave interference model based on imaginga contact lens disposed on an optical phantom with the OSI device inFIG. 14 and analyzing the optical wave interference in the specularlyreflected light returned from the contact lens disposed on the opticalphantom;

FIG. 53 is a schematic diagram of a contact lens disposed on an opticalphantom;

FIG. 54 is a flowchart of an exemplary process for determining tear filmcharacteristics of a patient's ocular tear film based on analysis of anon-contact lens-based region of interest of an image of a patient'stear film during contact lens wear, to determine the patient'sintolerance to contact lens wear.

DETAILED DESCRIPTION

The embodiments set forth below represent the necessary information toenable those skilled in the art to practice the disclosure andillustrate the best mode of practicing the disclosure. Upon reading thefollowing description in light of the accompanying drawing figures,those skilled in the art will understand the concepts of the disclosureand will recognize applications of these concepts not particularlyaddressed herein. It should be understood that these concepts andapplications fall within the scope of the disclosure and theaccompanying claims.

Methods and apparatuses for determining contact lens intolerance incontact lens wearer patients based on tear film characteristics analysisand dry eye symptoms are disclosed. An ocular tear film may be affectedby contact lens wear. Contact lens wear can contribute to dry eye. Acontact lens can disrupt the natural tear film and can reduce cornealsensitivity over time, which can cause a reduction in tear filmproduction. For many patients, evaporative dry eye disease is anunderlying cause for their contact lens intolerance. Thus, inembodiments herein, imaging of the ocular tear film is performed duringcontact lens wear. For example, the imaging may include captured opticalwave interference of specularly reflected light from the ocular tearfilm, when the ocular tear film is illuminated with the light source. Ananalysis of the image of the ocular tear film is performed to determineone or more tear film characteristics of the ocular tear film. The tearfilm characteristics can be used to determine the effect or possibleeffect of contact lens wear on the ocular tear film, and thus be used todetermine contact lens intolerance of the patient. As examples, the tearfilm characteristics used to analyze contact lens intolerance based onimages of the ocular tear film involving contact lens wear may includedry eye symptoms, including but not limited to tear film thickness, tearfilm viscosity, and tear film movement rate in the eye. When referringto tear film herein, it should be noted that such refers to the lipidlayer and/or the aqueous layer of the ocular tear film.

In this regard, FIGS. 4A-4B illustrate a general embodiment of an ocularsurface interferometry (OSI) device 30 that can be used to determinecontact lens intolerance in contact lens wearer patients based on tearfilm characteristics analysis and dry eye symptoms. In general, the OSIdevice 30 is configured to illuminate a patient's ocular tear film,capture images of interference interactions of specularly reflectedlight from the ocular tear film, and process and analyze theinterference interactions to determine tear film characteristics of acontact lens wearer patient. As shown in FIG. 4A, the exemplary OSIdevice 30 positioned in front of one of the patient's eye 32 is shownfrom a side view. A top view of the patient 34 in front of the OSIdevice 30 is illustrated in FIG. 4B. The ocular tear film of a patient'seyes 32 is illuminated with a light source 36 (also referred to hereinas “illuminator 36”) and comprises a large area light source having aspectrum in the visible region adequate for tear film layer thickness(TFLT) measurement and correlation to dry eye. The illuminator 36 can bea white or multi-wavelength light source.

In this embodiment, the illuminator 36 is a Lambertian emitter and isadapted to be positioned in front of the eye 32 on a stand 38. Asemployed herein, the terms “Lambertian surface” and “Lambertian emitter”are defined to be a light emitter having equal or substantially equal(also referred to as “uniform” or substantially uniform) intensity inall directions. This allows the imaging of a uniformly or substantiallyuniformly bright tear film region for determining tear filmcharacteristics of a contact lens wearer patient, as discussed in moredetail in this disclosure. The illuminator 36 could also be amulti-light wave illuminator or a mono-chromatic illuminator. Theilluminator 36 in this embodiment, comprises a large surface areaemitter, arranged such that rays emitted from the emitter are specularlyreflected from the ocular tear film and undergo constructive anddestructive interference in tear film layers therein. An image of thepatient's 34 lipid layer is the backdrop over which the interferenceimage is seen and it should be as spatially uniform as possible.

An imaging device 40 is included in the OSI device 30 and is employed tocapture interference interactions of specularly reflected light from thepatient's 34 ocular tear film when illuminated by the illuminator 36.The imaging device 40 may be a still or video camera, or other devicethat captures images and produces an output signal representinginformation in captured images. The output signal may be a digitalrepresentation of the captured images. The geometry of the illuminator36 can be understood by starting from an imaging lens 42 of the imagingdevice 40 and proceeding forward to the eye 32 and then to theilluminator 36. The fundamental equation for tracing ray lines isSnell's law, which provides:

n1 Sin Θ₁ =n2 Sin Θ₂,

where “n1” and “n2” are the indexes of refraction of two mediumscontaining the ray, and Θ₁ and Θ₂ is the angle of the ray relative tothe normal from the transition surface. As illustrated in FIG. 5, lightrays 44 are directed by the illuminator 36 to an ocular tear film 46. Inthe case of specularly reflected light 48 that does not enter a lipidlayer 50 and instead reflects from an anterior surface 52 of the lipidlayer 50, Snell's law reduces down to Θ₁=Θ₂, since the index ofrefraction does not change (i.e., air in both instances). Under theseconditions, Snell's law reduces to the classical law of reflection suchthat the angle of incidence is equal and opposite to the angle ofreflectance.

Some of the light rays 54 pass through the anterior surface 52 of thelipid layer 50 and enter into the lipid layer 50, as illustrated in FIG.5. As a result, the angle of these light rays 54 (i.e., Θ₃) normal tothe anterior surface 52 of the lipid layer 50 will be different than theangle of the light rays 44 (Θ₁) according to Snell's law. This isbecause the index of refraction of the lipid layer 50 is different thanthe index of refraction of air. Some of the light rays 54 passingthrough the lipid layer 50 will specularly reflect from the lipidlayer-to-aqueous layer transition 56 thereby producing specularlyreflected light rays 58. The specularly reflected light rays 48, 58undergo constructive and destructive interference anterior of the lipidlayer 50. The modulations of the interference of the specularlyreflected light rays 48, 58 superimposed on the anterior surface 52 ofthe lipid layer 50 are collected by the imaging device 40 when focusedon the anterior surface 52 of the lipid layer 50. Focusing the imagingdevice 40 on the anterior surface 52 of the lipid layer 50 allowscapturing of the modulated interference information at the plane of theanterior surface 52. In this manner, the captured interferenceinformation and the resulting determined tear film characteristics of acontact lens wearer patient from the interference information isspatially registered to a particular area of the tear film 46 since thedetermined tear film characteristics of a contact lens wearer patientcan be associated with such particular area, if desired.

The thickness of the lipid layer 50 (‘d₁’) is a function of theinterference interactions between specularly reflected light rays 48,58. The thickness of the lipid layer 50 (‘d₁’) is on the scale of thetemporal (or longitudinal) coherence of the light source 30. Therefore,thin lipid layer films on the scale of one wavelength of visible lightemitted by the light source 30 offer detectable colors from theinterference of specularly reflected light when viewed by a camera orhuman eye. The colors may be detectable as a result of calculationsperformed on the interference signal and represented as a digital valuesincluding but not limited to a red-green-blue (RGB) value in the RGBcolor space. Quantification of the interference of the specularlyreflected light can be used to measure LLT. Also, the change inthickness of the lipid layer over a period of time can be determined byevaluating the quantification of the interference of the specularlyreflected light over a predetermined period of time. The thicknesses ofan aqueous layer 60 (‘d₂’) can also be determined using the sameprinciple. Some of the light rays 54 (not shown) passing through thelipid layer 50 can also pass through the lipid-to-aqueous layertransition 56 and enter into the aqueous layer 60 specularly reflectingfrom the aqueous-to-mucin/cornea layer transition 62. These specularreflections also undergo interference with the specularly reflectedlight rays 48, 58. The magnitude of the reflections from each interfacedepends on the refractive indices of the materials as well as the angleof incidence, according to Fresnel's equations, and so the depth of themodulation of the interference interactions is dependent on theseparameters, thus so is the resulting color. Similarly, the change inthickness of the aqueous layer over a period of time can be determinedby evaluating the quantification of the interference of the specularlyreflected light over a predetermined period of time.

Turning back to FIGS. 4A and 4B, the illuminator 36 in this embodimentis a broad spectrum light source covering the visible region betweenabout 400 nm to about 700 nm. The illuminator 36 contains an arced orcurved housing 64 (see FIG. 4B) into which individual light emitters aremounted, subtending an arc of approximately 130 degrees from the opticalaxis of the eye 32 (see FIG. 4B). A curved surface may present betteruniformity and be more efficient, as the geometry yields a smallerdevice to generating a given intensity of light. The total powerradiated from the illuminator 36 should be kept to a minimum to preventaccelerated tear evaporation. Light entering the pupil can cause reflextearing, squinting, and other visual discomforts, all of which affecttear film characteristic measurements accuracy involving a patient withcontact lens wear.

In order to prevent alteration of the proprioceptive senses and reduceheating of the tear film 46, incident power and intensity on the eye 32may be minimized and thus, the step of collecting and focusing thespecularly reflected light may be carried out by the imaging device 40.The imaging device 40 may be a video camera, slit lamp microscope, orother observation apparatus mounted on the stand 38, as illustrated inFIGS. 4A and 4B. Detailed visualization of the image patterns of thetear film 46 involves collecting the specularly reflected light 66 andfocusing the specularly reflected light at the lipid layer 50 such thatthe interference interactions of the specularly reflected light from theocular tear film are observable.

Against the backdrop of the OSI device 30 in FIGS. 4A and 4B, FIG. 6illustrates a flowchart discussing how the OSI device 30 can be used toobtain interference interactions of specularly reflected light from thetear film 46, which can be used to determine tear film characteristicsin contact lens wearers. As previously discussed above, an ocular tearfilm may be affected by contact lens wear. Contact lens wear cancontribute to dry eye. A contact lens can disrupt the natural tear filmand can reduce corneal sensitivity over time, which can cause areduction in tear film production. For many of patients, evaporative dryeye disease is an underlying cause for their contact lens intolerance.Thus, in embodiments herein, imaging of the ocular tear film isperformed during contact lens wear.

In this regard, as illustrated in FIG. 6, the illuminator 36 of the OSIdevice 30 is employed to illuminate the ocular tear film of a patientwith a contact lens disposed on a patient's eye. The exemplary processwill be described followed by a more detailed discussion of the steps ofthe process. The process in this example starts by adjusting the patient32 with regard to an illuminator 36 and an imaging device 40 in the OSIdevice 30 in FIGS. 4A and 4B. The illuminator 36 is controlled toilluminate the patient's 34 tear film 46. The imaging device 40 iscontrolled to be focused on the anterior surface 52 of the lipid layer50 such that the interference interactions of specularly reflected lightfrom the tear film 46 are collected and are observable. Thereafter, thepatient's 34 tear film 46 is illuminated by the illuminator 36 (block 67in FIG. 6). The patient may be instructed to blink hard and/or hold ablink for a period of time, for example 15 seconds, prior toillumination and imaging, described below.

The imaging device 40 of the OSI device 30 is then controlled andfocused on the lipid layer 50 to capture specularly reflected light in afirst image from the ocular tear film with a contact lens disposed onthe patient's eye as a result of illuminating the tear film with theilluminator 36 in a first image (block 68, FIG. 6). The ocular tear filmis disposed on top of the contact lens. The first image contains opticalwave interference of specularly reflected light from the ocular tearfilm when illuminated by the illuminator 36. An example of such a firstimage by the imaging device 40 is provided in FIG. 7. As illustratedtherein, a first image 79 of a patient's eye 80 that has a contact lens84 disposed on the patient's eye 80 is shown that has been illuminatedwith the illuminator 36. The illuminator 36 and the imaging device 40may be controlled to illuminate an area or region of interest 81 on atear film 82 that does not include a pupil 83 of the eye 80 so as toreduce reflex tearing. Reflex tearing will temporarily lead to thickeraqueous and lipid layers, thus temporarily altering the interferencesignals of specularly reflected light from the tear film 82.

As shown in FIG. 7, when the imaging device 40 is focused on an anteriorsurface 86 of the lipid layer 88 of the tear film 82 disposed on top ofthe contact lens 84, interference interactions 85 of the interferencesignal of the specularly reflected light from the tear film 82 as aresult of illumination by the illuminator 36 are captured in the area orregion of interest 81 in the first image 79. The region of interest 81has a contact lens-based region 87 where the contact lens 84 was presentin the first image 79. The interference interactions 85 appear to ahuman observer as colored patterns as a result of the wavelengthspresent in the interference of the specularly reflected light from thetear film 82. As will be discussed in more detail below, it may bedesired to isolate the contact lens-based region 87 in the first image79 to analyze the specularly reflected light from the tear film 82 as aresult of illumination by the illuminator 36 in the contact lens-basedregion 87 and in the region of interest 81 where the contact lens 84 isnot present in the first image 79 (block 72 in FIG. 6). In this manner,effect of tear film characteristics due to the patient's wear of thecontact lens 84 may be determined and/or observed.

With continuing reference to FIG. 7, a background signal is alsocaptured in the first image 79. The background signal is added to thespecularly reflected light in the area or region of interest 81 andincluded outside the area or region of interest 81 as well. Backgroundsignal is light that is not specularly reflected from the tear film 82and thus contains no interference information. Background signal caninclude stray and ambient light entering into the imaging device 40,scattered light from the patient's 34 face, eyelids, and/or eye 80structures outside and beneath the tear film 82 as a result of straylight, ambient light and diffuse illumination by the illuminator 36, andimages of structures beneath the tear film 82. For example, the firstimage 79 includes the iris of the eye 80 beneath the tear film 82.Background signal adds a bias (i.e., offset) error to the capturedinterference of specularly reflected light from the tear film 82 therebyreducing its signal strength and contrast. Further, if the backgroundsignal has a color hue different from the light of the light source, acolor shift can also occur to the interference of specularly reflectedlight from the tear film 82 in the first image 79. The imaging device 40produces a first output signal that represents the light rays capturedin the first image 79. Because the first image 79 contains light raysfrom specularly reflected light as well as the background signal, thefirst output signal produced by the imaging device 40 from the firstimage 79 will contain an interference signal representing the capturedinterference of the specularly reflected light from the tear film 82with a bias (i.e., offset) error caused by the background signal. As aresult, the first output signal analyzed to determine tear filmcharacteristic determinations and/or measurements involving a patientwith contact lens wear may contain error as a result of the backgroundsignal bias (i.e., offset) error.

Thus, in this embodiment, the first output signal generated by theimaging device 40 as a result of the first image 79 is processed tosubtract or substantially subtract the background signal from theinterference signal to reduce error before being analyzed to determinetear film characteristic determinations and/or measurements involving apatient with contact lens wear. This is also referred to as “backgroundsubtraction.” Background subtraction is the process of removing unwantedreflections from images. In this regard, the imaging device 40 isoptionally controlled to capture a second, background image 90 (“secondimage 90”) of the tear film 82 when not illuminated by the illuminator36, as illustrated by example in FIG. 8 (block 70 in FIG. 6). The secondimage 90 can be captured using the same imaging device 40 settings andfocal point as when capturing the first image 79 so that the first image79 and second image 90 forms corresponding image pairs captured within ashort time of each other. The imaging device 40 produces a second outputsignal containing background signal present in the first image 79. Toeliminate or reduce this background signal from the first output signal,the second output signal is subtracted from the first output signal toproduce a resulting signal (block 71 in FIG. 6). The image representingthe resulting signal in this example is illustrated in FIG. 9 asresulting image 92. Thus, in this example, background subtractioninvolves two images 79, 90 to provide a frame pair where the two images79, 90 are subtracted from each other, whereby specular reflection fromthe tear film 82 is retained, and while diffuse reflections from theiris and other areas are removed in whole or part.

As illustrated in FIG. 9, the resulting image 92 contains an image ofthe isolated interference 94 of the specularly reflected light from thetear film 82 with the background signal eliminated or reduced (block 71in FIG. 6). In this manner, the resulting signal (representing theresulting image 92 in FIG. 9) includes an interference signal havingsignal improved purity and contrast in the area or region of interest 81on the tear film 82. As will be discussed later in this application, theresulting signal provides for accurate analysis of interferenceinteractions from the interference signal of specular reflections fromthe tear film 82 to in turn determine more tear film characteristicsindicative of contact lens wear intolerance. Any method or device toobtain the first and second images of the tear film 82 and perform thesubtraction of background signal in the second image 90 from the firstimage 79 may be employed. Other specific examples are discussedthroughout the remainder of this application.

An optional registration function may be performed between the firstimage(s) 79 and the second image(s) 90 before subtraction is performedto ensure that an area or point in the second image(s) 90 to besubtracted from the first image(s) 79 is for an equivalent orcorresponding area or point on the first image(s) 79. For example, a setof homologous points may be taken from the first and second images 79,90 to calculate a rigid transformation matrix between the two images.The transformation matrix allows one point on one image (e.g., x1, y1)to be transformed to an equivalent two-dimensional (2D) image on theother image (e.g., x2, y2). For example, the Matlab® function “cp2tform”can be employed in this regard. Once the transformation matrix isdetermined, the transformation matrix can be applied to every point inthe first and second images, and then each re-interpolated at theoriginal points. For example, the Matlab® function “imtransform” can beemployed in this regard. This allows a point from the second image 90(e.g., x2, y2) to be subtracted from the correct, equivalent point(e.g., x1, y1) on the first image(s) 79, in the event there is anymovement in orientation or the patient's eye between the capture of thefirst and second images 79, 90. The first and second images 79, 90should be captured close in time.

Note that while this example discusses a first image and a second (i.e.,background) image captured by the imaging device 40 and a resultingfirst output signal and second output signal, the first image and thesecond image may comprise a plurality of images taken in atime-sequenced fashion. If the imaging device 40 is a video camera, thefirst and second images may contain a number of sequentially-timedframes governed by the frame rate of the imaging device 40. The imagingdevice 40 produces a series of first output signals and second outputsignals. If more than one image is captured, the subtraction performedin a first image should ideally be from a second image taken immediatelyafter the first image so that the same or substantially the samelighting conditions exist between the images so the background signal inthe second image is present in the first image. The subtraction of thesecond output signal from the first output signal can be performed inreal time. Alternatively, the first and second output signals can berecorded and processed at a later time. The illuminator 36 may becontrolled to oscillate off and on quickly so that first and secondimages can be taken and the second output signal subtraction from thefirst output signal be performed in less than one second. For example,if the illuminator 36 oscillates between on and off at 30 Hz, theimaging device 40 can be synchronized to capture images of the tear film46 at 60 frames per second (fps). In this regard, thirty (30) firstimages and thirty (30) second images can be obtained in one second, witheach pair of first and second images taken sequentially.

After the interference of the specularly reflected light is captured anda resulting signal containing the interference signal is produced andprocessed, the contact lens-based region of interest 87 is isolated fromthe resulting image 92 (block 72 in FIG. 6) as shown in FIG. 10. Theinterference signal or representations thereof in the contact lens-basedregions of interest 87 can be converted to at least one color-basedvalue (block 73 in FIG. 6) and compared against a lipid layer-contactlens layer interference model that includes a contact lens index ofrefraction as part of the aqueous layer in the model (block 74 in FIG.6) to determine one or more tear film characteristics (block 75 in FIG.6), such as measuring tear film thickness, as will be discussed in moredetail below. The interference signal can be processed and converted bythe imaging device into digital red-green-blue (RGB) component valueswhich can be compared to RGB component values in a tear filminterference model to determine tear film characteristics of the contactlens-based regions of interest 87.

The lipid layer-contact lens layer interference model is based onmodeling the lipid layer of the tear film in various LLTs with thepresence of a contact lens and representing resulting interferenceinteractions in the interference signal of specularly reflected lightfrom the model when illuminated by the light source. The lipidlayer-contact lens layer interference model can be a theoretical tearfilm interference model where the particular light source, theparticular imaging device, and the tear film layers are modeledmathematically, and the resulting interference signals for the variousLLTs recorded when the modeled light source illuminates the modeled tearfilm layers recorded using the modeled imaging device. The settings forthe mathematically modeled light source and imaging device should bereplicated in the illuminator 36 and imaging device 40 used in the OSIdevice 30. Alternatively, as will be discussed in more detail below, thelipid layer-contact lens layer interference model can be based on aphantom tear film model, comprised of physical phantom tear film layerswherein the actual light source is used to illuminate the phantom tearfilm model and interference interactions in the interference signalrepresenting interference of specularly reflected light are empiricallyobserved and recorded using the actual imaging device 40.

The aqueous layer may be modeled in the lipid layer-contact lens layerinterference model to be of an infinite, minimum, or varying thicknessbased on the index of refraction of the contact lens. If the aqueouslayer is modeled to be of an infinite thickness, the lipid layer-contactlens layer interference model assumes no specular reflections occur fromthe aqueous (i.e. contact lens)-to-mucin layer transition 62 (see FIG.5). If the contact lens is modeled to be of a certain minimum thickness(e.g., ≧2 μm), the specular reflection from the aqueous (contactlens)-to-mucin layer transition 62 may be considered negligible on theeffect of the convolved RGB signals produced by the interference signal.In either case, the lipid layer-contact lens layer interference modelwill only assume and include specular reflections from thelipid-to-aqueous layer transition 56. Thus, these lipid layer-contactlens layer interference model embodiments allow the determining of tearfilm characteristics of the contact lens-based region of interest 87regardless of ALT. The interference interactions in the interferencesignal are compared to the interference interactions in the lipidlayer-contact lens layer interference model to determine tear filmcharacteristics of the contact lens-based region of interest 87.

Alternatively, if the contact lens representing the aqueous layer 60 ismodeled to be of varying thicknesses, the lipid layer-contact lens layerinterference model additionally includes specular reflections from theaqueous (contact lens)-to-mucin layer transition 62 in the interferenceinteractions. As a result, the lipid layer-contact lens layerinterference model will include two-dimensions of data comprised ofinterference interactions corresponding to various LLT and ALTcombinations. The interference interactions from the interference signalcan be compared to interference interactions in the lipid layer-contactlens layer interference model to measure both LLT and ALT. Moreinformation regarding specific tear film interference models will bedescribed later in this application.

In the above described embodiment in FIGS. 6-9, the second image 90 ofthe tear film 82 containing background signal is captured when notilluminated by the illuminator 36. Only ambient light illuminates thetear film 82 and eye 80 structures beneath. Thus, the second image 90and the resulting second output signal produced by the imaging device 40from the second image 90 does not include background signal resultingfrom scattered light from the patient's 34 face and eye structures as aresult of diffuse illumination by the illuminator 36. Only scatteredlight resulting from ambient light is included in the second image 90.However, scattered light resulting from diffuse illumination by theilluminator 36 is included in background signal in the first image 79containing the interference interactions of specularly reflected lightfrom the tear film 82. Further, because the first image 79 is capturedwhen the illuminator 36 is illuminating the tear film 82, the intensityof the eye structures beneath the tear film 82 captured in the firstimage 79, including the iris, are brighter than captured in the secondimage 90.

Thus, in other embodiments described herein, the imaging device 40 iscontrolled to capture a second image 90 of the tear film 82 whenobliquely illuminated by the illuminator 36. As a result, the capturedsecond image 90 additionally includes background signal from scatteredlight as a result of diffuse illumination by the illuminator 36 as wellas a higher intensity signal of the directly illuminated eye structuresbeneath the tear film 82. Thus, when the second output signal issubtracted from the first output signal, the higher intensity eyestructure background and the component of background signal representingscattered light as a result of diffuse illumination by the illuminator36, as well as ambient and stray light, are subtracted or substantiallysubtracted from the resulting signal thereby further increasing theinterference signal purity and contrast in the resulting signal. Theresulting signal can then be processed and analyzed to determine tearfilm characteristics of a patient involving contact lens wear, as willbe described in detail later in this application.

In this regard, FIGS. 11-13 illustrate an embodiment for illuminatingand capturing interference of specularly reflected light from the tearfilm. In this embodiment, the second image is captured when the tearfilm is obliquely illuminated by the illuminator 36 using illuminationthat possesses the same or nearly the same average geometry andilluminance level as used to produce specularly reflected light from atear film. In this manner, the background signal captured in the secondimage contains the equivalent background signal present in the firstimage including scattered light from the tear film and patient's eye asa result of diffuse illumination by the illuminator 36. The second imagealso includes a representative signal of eye structure beneath the tearfilm because of the equivalent lighting when the illuminator 36 isactivated when capturing the second image. In this embodiment, a “tiled”or “tiling” illumination of the tear film is provided. Tiling allows alight source to illuminate a sub-area(s) of interest on the tear film toobtain specularly reflected light while at the same time diffuselyilluminating adjacent sub-area(s) of interest of the tear film to obtainscattered light as a result of diffuse illumination by the illuminator36. In this manner, the subtracted background signal includes scatteredlight as a result of diffuse illumination by the illuminator 36 to allowfurther reduction of offset bias (i.e., offset) error and to therebyincrease interference signal purity and contrast.

In this regard, the illuminator 36 is controlled to illuminate thepatient's 34 tear film. The imaging device 40 is located appropriatelyand is controlled to be focused on the lipid layer such that theinterference interactions of specularly reflected light from the tearfilm are observable when the tear film is illuminated. Thereafter, thelighting pattern of the illuminator 36 is controlled in a first “tiling”mode to produce specularly reflected light from a first area(s) ofinterest of the tear film while diffusely illuminating an adjacent,second area(s) of interest of the tear film. As will be discussed inmore detail later in this application, the illuminator 36 may becontrolled to turn on only certain lighting components in theilluminator 36 to control the lighting pattern. As will be furtherdiscussed, the lighting pattern can also be directed to the meibomianglands directly, the transillumination of the meibomian glands, and thecharacteristics of the patient's blinking or partial blinking.

An example of a first image 120 captured of a patient's eye 121 and tearfilm 123 by the imaging device 40 when the illuminator 36 produces alight pattern in the first mode is illustrated by example in FIG. 11. Inthis example, the illuminator 36 is controlled to provide a first tiledillumination pattern in an area or region of interest 122 on the tearfilm 123. While illumination of the tear film 123 occurs in the firstmode, the imaging device 40 captures the first image 120 of thepatient's eye 121 and the tear film 123. As illustrated in FIG. 11, thefirst image 120 of the patient's eye 121 has been illuminated so thatspecularly reflected light is produced in first portions 126A in thearea or region of interest 122 of the tear film 123. The interferencesignal(s) from the first portions 126A include interference fromspecularly reflected light along with additive background signal, whichincludes scattered light signal as a result of diffuse illumination fromthe illuminator 36. Again, the illuminator 36 and the imaging device 40may be controlled to illuminate the tear film 123 that does not includethe pupil of the eye 121 so as to reduce reflex tearing. The illuminator36 may be flashed in to produce specularly reflected light from thefirst portions 126A, whereby the imaging device 40 is synchronized withthe flashing of the illuminator 36 in to capture the first image 120 ofthe patient's eye 121 and the tear film 123.

Also during the first mode, the illuminator 36 light pattern obliquelyilluminates second, adjacent portions 128A to the first portions 126A inthe area or region of interest 122, as shown in the first image 120 inFIG. 11. The second portions 128A include comparable background offsetpresent in the first portion(s) 126A, which includes scattered lightsignal as a result of diffuse illumination from the illuminator 36 sincethe illuminator 36 is turned on when the first image 120 is captured bythe imaging device 40. Further, the eye 121 structures beneath the tearfilm 123 are captured in the second portions 128A due to the diffuseillumination by the illuminator 36. This is opposed to the second image90 of FIG. 9, where diffuse illumination by the illuminator 36 is notprovided to the tear film when the second image 90 is obtained. Thus, inthis embodiment, the area or region of interest 122 of the tear film 123is broken into two portions at the same time: first portions 126Aproducing specularly reflected light combined with background signal,and second portions 128A diffusedly illuminated by the illuminator 36and containing background signal, which includes scattered light fromthe illuminator 36. The imaging device 40 produces a first output signalthat contains a representation of the first portions 126A and the secondportions 128A.

Next, the illuminator 36 is controlled in a second mode to reverse thelighting pattern from the first mode when illuminating the tear film123. A second image 130 is captured of the tear film 123 is captured inthe second mode of illumination, as illustrated by example in FIG. 12.As shown in the second image 130 in FIG. 12, the second portions 128A inthe first image 120 of FIG. 11 are now second portions 128B in thesecond image 130 in FIG. 12 containing specularly reflected light fromthe tear film 123 with additive background signal. The first portions126A in the first image 120 of FIG. 11 are now first portions 126B inthe second image 130 in FIG. 12 containing background signal withoutspecularly reflected light. Again, the background signal in the firstportions 126B includes scattered light signal as a result of diffuseillumination by the illuminator 36. The imaging device 40 produces asecond output signal of the second image 130 in FIG. 12. The illuminator36 may also be flashed in block 106 to produce specularly reflectedlight from the second portions 128B, whereby the imaging device 40 issynchronized with the flashing of the illuminator 36 to capture thesecond image 130 of the patient's eye 121 and the tear film 123.

The first and second output signals can then be combined to produce aresulting signal comprised of the interference signal of the specularlyreflected light from the tear film 123 with background signal subtractedor substantially removed from the interference signal. A resulting imageis produced as a result of having interference information from thespecularly reflected light from the area or region of interest 122 ofthe tear film 123 with background signal eliminated or reduced,including background signal resulting from scattered light from diffuseillumination by the illuminator 36. An example of a resulting image 132in this regard is illustrated in FIG. 13. The resulting image 132represents the first output signal represented by the first image 120 inFIG. 11 combined with the second output signal represented by the secondimage 130 in FIG. 12. As illustrated in FIG. 13, interference signals ofspecularly reflected light from the tear film 123 are provided for boththe first and second portions 126, 128 in the area or region of interest122. The background signal has been eliminated or reduced. As can beseen in FIG. 13, the signal purity and contrast of the interferencesignal representing the specularly reflected light from the tear film123 from first and second portions 126, 128 appears more vivid andhigher in contrast than the interference interaction 94 in FIG. 9, forexample.

In the discussion of the example first and second images 120, 130 inFIGS. 11 and 12 above, each first portion 126 can be thought of as afirst image, and each second portion 128 can be thought of as a secondimage. Thus, when the first and second portions 126A, 128B are combinedwith corresponding first and second portions 126B, 128A, this is akin tosubtracting second portions 126B, 128A from the first portions 126A,128B, respectively.

In the example of FIGS. 11-13, the first image and second images 120,130 contain a plurality of portions or tiles. The number of tilesdepends on the resolution of lighting interactions provided for andselected for the illuminator 36 to produce the first and second modes ofillumination to the tear film 123. The illumination modes can go fromone extreme of one tile to any number of tiles desired. Each tile can bethe size of one pixel in the imaging device 40 or areas covering morethan one pixel depending on the capability of the illuminator 36 and theimaging device 40. The number of tiles can affect accuracy of theinterference signals representing the specularly reflected light fromthe tear film. Providing too few tiles in a tile pattern can limit therepresentative accuracy of the average illumination geometry thatproduces the scattered light signal captured by the imaging device 40 inthe portions 128A and 126B for precise subtraction from portions 128Band 126A respectively.

Note that while this example in FIGS. 11-13 discusses a first image anda second image captured by the imaging device 40 and a resulting firstoutput signal and second output signal, the first image and the secondimage may comprise a plurality of images taken in a time-sequencedfashion. If the imaging device 40 is a video camera, the first andsecond images may contain a number of sequentially-timed frames governedby the frame rate of the imaging device 40. The imaging device 40produces a series of first output signals and second output signals. Ifmore than one image is captured, the subtraction performed in a firstimage should ideally be from a second image taken immediately after thefirst image so that the same or substantially the same lightingconditions exist between the images so the background signal in thesecond image is present in the first image, and more importantly, sothat movement of the eye and especially of the tear-film dynamic isminimal between subtracted frames. The subtraction of the second outputsignal from the first output signal can be performed in real time.Alternatively, the first and second output signals can be recorded andprocessed at a later time.

The first and second output signals can then be combined to produce aresulting signal comprised of the interference signal of the specularlyreflected light from the tear film 142 for the entire area or region ofinterest 146 with background signal subtracted or substantially removedfrom the interference signal. A resulting image (not shown) similar toFIG. 12 can be produced as a result of having interference informationfrom the specularly reflected light from the area or region of interest146 from the tear film 142 with background signal eliminated or reduced,including background signal resulting from scattered light from diffuseillumination by the illuminator 36.

The resulting image can then be processed and analyzed to determine tearfilm characteristics of a contact lens wearing patient. The processesdescribed above in FIG. 6 of isolating a contact lens-based region ofinterest 127 in the region of interest 122 to determine tear filmcharacteristics therein can be employed.

Exemplary OSI Device

The above discussed illustrations provide examples of illuminating andimaging a patient's tear film involving contact lens wear. Theseprinciples are described in more detail with respect to a specificexample of an OSI device 170 illustrated in FIG. 14 and described belowthroughout the remainder of this application. The OSI device 170 canilluminate a patient's tear film, capture interference information fromthe patient's tear film, and process and analyze the interferenceinformation to measure tear film characteristics involving contact lenswear by a patient, including but not limited to TFLT. Tear filmcharacteristics may include size, shape, movement or speed, break up ordisappearance of tear film, spread or coverage within an area ofinterest, and consistency of TFLT within an area of interest. Further,the OSI device 170 includes a number of optional pre-processing featuresthat may be employed to process the interference signal in the resultingsignal to enhance tear film characteristic determinations and/ormeasurements. The OSI device 170 may include a display and userinterface to allow a physician or technician to control the OSI device170 to image a patient's eye and tear film and determine and/or measuretear film characteristic involving contact lens wear by a patient.

Illumination and Imaging

In this regard, FIG. 14 illustrates a perspective view of the OSI device170. The OSI device 170 is designed to facilitate imaging of thepatient's ocular tear film and processing and analyzing the images todetermine characteristics regarding a patient's tear film. The OSIdevice 170 includes an imaging device and light source in this regard,as will be described in more detail below. As illustrated in FIG. 14,the OSI device 170 is comprised generally of a housing 172, a displaymonitor (“display”) 174, and a patient head support 176. The housing 172may be designed for table top placement. The housing 172 rests on a base178 in a fixed relationship. As will be discussed in more detail below,the housing 172 houses an imaging device and other electronics,hardware, and software to allow a clinician to image a patient's oculartear film. A light source 173 (also referred to herein as “illuminator173”) is also provided in the housing 172 and provided behind adiffusing translucent window 175. The translucent window 175 may be aflexible, white, translucent acrylic plastic sheet.

To image a patient's ocular tear film, the patient places his or herhead in the patient head support 176 and rests his or her chin on a chinrest 180. The chin rest 180 can be adjusted to align the patient's eyeand tear film with the imaging device inside the housing 172, as will bediscussed in more detail below. The chin rest 180 may be designed tosupport up to two (2) pounds of weight, but such is not a limitingfactor. A transparent window 177 allows the imaging device inside thehousing 172 to have a clear line of sight to a patient's eye and tearfilm when the patient's head is placed in the patient head support 176.The OSI device 170 is designed to image one eye at a time, but can beconfigured to image both eyes of a patient, if desired.

In general, the display 174 provides input and output from the OSIdevice 170. For example, a user interface can be provided on the display174 for the clinician to operate the OSI device 170 and to interact witha control system provided in the housing 172 that controls the operationof the OSI device 170, including an imaging device, an imaging devicepositioning system, a light source, other supporting hardware andsoftware, and other components. For example, the user interface canallow control of imaging positioning, focus of the imaging device, andother settings of the imaging device for capturing images of a patient'socular tear film. The control system may include a general purposemicroprocessor or computer with memory for storage of data, includingimages of the patient's eye and tear film. The microprocessor should beselected to provide sufficient processing speed to process images of thepatient's tear film and generate output characteristic information aboutthe tear film (e.g., one minute per twenty second image acquisition).The control system may control synchronization of activation of thelight source and the imaging device to capture images of areas ofinterest on the patient's ocular tear film when properly illuminated.Various input and output ports and other devices can be provided,including but not limited to a joystick for control of the imagingdevice, USB ports, wired and wireless communication including Ethernetcommunication, a keyboard, a mouse, speaker(s), etc. A power supply isprovided inside the housing 172 to provide power to the componentstherein requiring power. A cooling system, such as a fan, may also beprovided to cool the OSI device 170 from heat generating componentstherein.

The display 174 is driven by the control system to provide tear filmcharacteristics regarding a patient's imaged tear film involving contactlens wear, including but not limited to TFLT. The display 174 alsoprovides a graphical user interface (GUI) to allow a clinician or otheruser to control the OSI device 170. To allow for human diagnosis of thepatient's tear film, images of the patient's ocular tear film taken bythe imaging device in the housing 172 can also be displayed on thedisplay 174 for review by a clinician, as will be illustrated anddescribed in more detail below. The images displayed on the display 174may be real-time images being taken by the imaging device, or may bepreviously recorded images stored in memory. To allow for differentorientations of the OSI device 170 to provide a universal configurationfor manufacturing, the display 174 can be rotated about the base 178.The display 174 is attached to a monitor arm 182 that is rotatable aboutthe base 178, as illustrated. The display 174 can be placed opposite ofthe patient head support 176, as illustrated in FIG. 14, if theclinician desires to sit directly across from the patient.Alternatively, display 174 can be rotated either left or right about theX-axis to be placed adjacent to the patient head support 176. Thedisplay 174 may be a touch screen monitor to allow a clinician or otheruser to provide input and control to the control system inside thehousing 172 directly via touch of the display 174 for control of the OSIdevice 170. The display 174 illustrated in FIG. 14 is a fifteen inch(15″) flat panel liquid crystal display (LCD). However, the display 174may be provided of any type or size, including but not limited to acathode ray tube (CRT), plasma, LED, OLED, projection system, etc.

FIG. 15 illustrates a side view of the OSI device 170 of FIG. 14 tofurther illustrate imaging of a patient's eye and ocular tear film. Asillustrated therein, a patient places their head 184 in the patient headsupport 176. More particularly, the patient places their forehead 186against a headrest 188 provided as part of the patient head support 176.The patient places their chin 190 in the chin rest 180. The patient headsupport 176 is designed to facilitate alignment of a patient's eye 192with the OSI device 170, and in particular, an imaging device 194 (andilluminator) shown as being provided inside the housing 172. The chinrest 180 can be adjusted higher or lower to move the patient's eye 192with respect to the OSI device 170.

As shown in FIG. 16, the imaging device 194 is used to image thepatient's ocular tear film to determine characteristics of the patient'stear film. In particular, the imaging device 194 is used to captureinterference interactions of the specularly reflected light from thepatient's tear film when illuminated by a light source 196 (alsoreferred to herein as “illuminator 196”) as well as background signal.As previously discussed, background signal may be captured when theilluminator 196 is illuminating or not illuminating a patient's tearfilm. In the OSI device 170, the imaging device 194 is the “The ImagingSource” model DFK21BU04 charge coupling device (CCD) digital videocamera 198, but many types of metrological grade cameras or imagingdevices can be provided. A CCD camera enjoys characteristics ofefficient light gathering, linear behavior, cooled operation, andimmediate image availability. A linear imaging device is one thatprovides an output signal representing a captured image which isprecisely proportional to the input signal from the captured image.Thus, use of a linear imaging device (e.g., gamma correction set to 1.0,or no gamma correction) provides undistorted interference data which canthen be analyzed using linear analysis models. In this manner, theresulting images of the tear film do not have to be linearized beforeanalysis, thus saving processing time. Gamma correction can then beadded to the captured linear images for human-perceptible display on anon-linear display 174 in the OSI device 170. Alternatively, theopposite scenario could be employed. That is, a non-linear imagingdevice or non-linear setting would be provided to capture tear filmimages, wherein the non-linear data representing the interferenceinteractions of the interference signal can be provided to a non-lineardisplay monitor without manipulation to display the tear film images toa clinician. The non-linear data would be linearized for tear filmprocessing and analysis to estimate tear film layer thickness.

The video camera 198 is capable of producing lossless full motion videoimages of the patient's eye. As illustrated in FIG. 16, the video camera198 has a depth of field defined by the angle between rays 199 and thelens focal length that allows the patient's entire tear film to be infocus simultaneously. The video camera 198 has an external triggersupport so that the video camera 198 can be controlled by a controlsystem to image the patient's eye. The video camera 198 includes a lensthat fits within the housing 172. The video camera 198 in thisembodiment has a resolution of 640×480 pixels and is capable of framerates up to sixty (60) frames per second (fps). The lens system employedin the video camera 198 images a 16×12 mm dimension in a sample planeonto an active area of a CCD detector within the video camera 198. As anexample, the video camera 198 may be the DBK21AU04 Bayer VGA (640×480)video camera using a Pentax VS-LD25 Daitron 25-mm fixed focal lengthlens. Other camera models with alternate pixel size and number,alternate lenses, (etc) may also be employed.

Although a video camera 198 is provided in the OSI device 170, a stillcamera could also be used if the frame rate is sufficiently fast enoughto produce high quality images of the patient's eye. High frame rate inframes per second (fps) facilitate high quality subtraction ofbackground signal from a captured interference signal representingspecularly reflected light from a patient's tear film, and may provideless temporal (i.e., motion) artifacts (e.g., motion blurring) incaptured images, resulting in high quality captured images. This isespecially the case since the patient's eye may move irregularly as wellas blinking, obscuring the tear film from the imaging device duringexamination.

A camera positioning system 200 is also provided in the housing 172 ofthe OSI device 170 to position the video camera 198 for imaging of thepatient's tear film. The camera positioning system 200 is under thecontrol of a control system. In this manner, a clinician can manipulatethe position of the video camera 198 to prepare the OSI device 170 toimage the patient's tear film. The camera positioning system 200 allowsa clinician and/or control system to move the video camera 198 betweendifferent patients' eyes 192, but can also be designed to limit therange of motion within designed tolerances. The camera positioningsystem 200 also allows for fine tuning of the video camera 198 position.The camera positioning system 200 includes a stand 202 attached to abase 204. A linear servo or actuator 206 is provided in the camerapositioning system 200 and connected between the stand 202 and a cameraplatform 207 supporting the video camera 198 to allow the video camera198 to be moved in the vertical (i.e., Y-axis) direction.

In this embodiment of the OSI device 170, the camera positioning system200 may not allow the video camera 198 to be moved in the X-axis or theZ-axis (in and out of FIG. 16), but the invention is not so limited. Theilluminator 196 is also attached to the camera platform 207 such thatthe illuminator 196 maintains a fixed geometric relationship to thevideo camera 198. Thus, when the video camera 198 is adjusted to thepatient's eye 192, the illuminator 196 is automatically adjusted to thepatient's eye 192 in the same regard as well. This may be important toenforce a desired distance (d) and angle of illumination (Φ) of thepatient's eye 192, as illustrated in FIG. 16, to properly capture theinterference interactions of the specularly reflected light from thepatient's tear film at the proper angle of incidence according toSnell's law, since the OSI device 170 is programmed to assume a certaindistance and certain angles of incidence. In the OSI device 170 in FIG.16, the angle of illumination (Φ) of the patient's eye 192 relative tothe camera 198 axis is approximately 30 degrees at the center of theilluminator 196 and includes a relatively large range of angles fromabout 5 to 60 degrees, but any angle may be provided.

System Level

Now that the imaging and illumination functions of the OSI device 170have been described, FIG. 17 illustrates a system level diagramillustrating more detail regarding the control system and other internalcomponents of the OSI device 170 provided inside the housing 172according to one embodiment to capture images of a patient's tear filmand process those images. As illustrated therein, a computer controlsystem 240 is provided that provides the overall control of the OSIdevice 170. The computer control system 240 may be provided by anymicroprocessor-based or computer system. The computer control system 240illustrated in FIG. 17 is provided in a system-level diagram and doesnot necessarily imply a specific hardware organization and/or structure.As illustrated therein, the computer control system 240 contains severalsystems. A camera settings system 242 may be provided that acceptscamera settings from a clinician user. Exemplary camera settings 244 areillustrated, but may be any type according to the type and model ofcamera provided in the OSI device 170 as is well understood by one ofordinary skill in the art.

The camera settings 244 may be provided to (The Imaging Source) cameradrivers 246, which may then be loaded into the video camera 198 uponinitialization of the OSI device 170 for controlling the settings of thevideo camera 198. The settings and drivers may be provided to a buffer248 located inside the video camera 198 to store the settings forcontrolling a CCD 250 for capturing ocular image information from a lens252. Ocular images captured by the lens 252 and the CCD 250 are providedto a de-Bayering function 254 which contains an algorithm forpost-processing of raw data from the CCD 250 as is well known. Theocular images are then provided to a video acquisition system 256 in thecomputer control system 240 and stored in memory, such as random accessmemory (RAM) 258. The stored ocular images or signal representations canthen be provided to a pre-processing system 260 and a post-processingsystem 262 to manipulate the ocular images to obtain the interferenceinteractions of the specularly reflected light from the tear film andanalyze the information to determine characteristics of the tear film.Pre-processing settings 264 and post-processing settings 266 can beprovided to the pre-processing system 260 and post-processing system262, respectively, to control these functions. These settings 264, 266will be described in more detail below. The post-processed ocular imagesand information may also be stored in mass storage, such as disk memory268, for later retrieval and viewing on the display 174.

The computer control system 240 may also contain a visualization system270 that provides the ocular images to the display 174 to be displayedin human-perceptible form on the display 174. Before being displayed,the ocular images may have to be pre-processed in a pre-processing videofunction 272. For example, if the ocular images are provided by a linearcamera, non-linearity (i.e. gamma correction) may have to be added inorder for the ocular images to be properly displayed on the display 174.Further, contrast and saturation display settings 274, which may becontrolled via the display 174 or a device communicating to the display174, may be provided by a clinician user to control the visualization ofocular images displayed on the display 174. The display 174 is alsoadapted to display analysis result information 276 regarding thepatient's tear film, as will be described in more detail below. Thecomputer control system 240 may also contain a user interface system 278that drives a graphical user interface (GUI) utility 280 on the display174 to receive user input 282. The user input 282 can include any of thesettings for the OSI device 170, including the camera settings 244, thepre-processing settings 264, the post-processing settings 266, thedisplay settings 274, the visualization system 270 enablement, and videoacquisition system 256 enablement, labeled 1-6. The GUI utility 280 mayonly be accessible by authorized personnel and used for calibration orsettings that would normally not be changed during normal operation ofthe OSI device 170 once configured and calibrated.

Overall Process Flow

FIG. 18 illustrates an exemplary overall flow process performed by theOSI device 170 for capturing tear film images from a patent and analysisfor determining tear film characteristics of a contact lens wearerpatient. As illustrated in FIG. 18, the video camera 198 is connectedvia a USB port 283 to the computer control system 240 (see FIG. 17) forcontrol of the video camera 198 and for transferring images of apatient's tear film taken by the video camera 198 back to the computercontrol system 240. The computer control system 240 includes acompatible camera driver 246 to provide a transfer interface between thecomputer control system 240 and the video camera 198. Prior to tear filmimage capture, the configuration or camera settings 244 are loaded intothe video camera 198 over the USB port 283 to prepare the video camera198 for tear film image capture (block 285). Further, an audio videointerleaved (AVI) container is created by the computer control system240 to store video of tear film images to be captured by the videocamera 198 (block 286). At this point, the video camera 198 and computercontrol system 240 are ready to capture images of a patient's tear film.The computer control system 240 waits for a user command to initiatecapture of a patient's tear film (blocks 287, 288).

Autopositioning and Autofocus

Before the computer control system 240 directs the video camera 198 ofthe OSI device 170 in FIG. 16 to capture images of the patient's tearfilm, it may be desired to position and focus the video camera 198 toobtain the most accurate images of the patient's tear film possible formore accurate analysis. Positioning the video camera 198 involvespositioning the lens of the video camera 198 in the Y-axis and Z-axisdirections, as shown in FIG. 16, to be in the desired alignment with thepatient's eye 192 and tear film to capture an image in a region ofinterest of the patient's tear film. As previously discussed above, itmay be desired to position the video camera 198 to capture specularlyreflected light from a portion of the tear film that is outside of thepupil area of the patient's eye 192. Focusing the video camera 198 meanschanging the focal length of the lens of the video camera 198 of the OSIdevice 170 in the X-axis directions, as shown in FIG. 16. Changing thefocus of the video camera 198 changes the point of convergence of thespecularly reflected light returned from the tear film of the patient'seye 192. Ideally, for a non-distorted image of the tear film of thepatient's eye 192, the focal length should be set for the specularlyreflected light returned from the tear film of the patient's eye 192 toconverge at an imaging plane of the video camera 198.

The technician can position the video camera 198 in alignment with thepatient's eye and tear film to be imaged. However, this introduces humanerror and/or involves trial and error by the technician, which may betime consuming. Further, as the OSI device 170 is used to imagedifferent eyes of the same patient, or a new patient, the video camera198 may need to be re-positioned each time. Thus, in embodimentsdisclosed herein, the video camera 198 can be autopositioned by the OSIdevice 170. In this regard, the computer control system 240 in FIG. 17can be programmed to autoposition the video camera 198 when desired. Forexample, it may be desired for the computer control system 240 to beprogrammed to autoposition the video camera 198 prior to step 287 inFIG. 18, where the video camera 198 and supporting components forstoring images of the patient's eye 192 are being configured andinitialized.

With reference back to FIG. 18, once image capture is initiated (block288), the computer control system 240 enables image capture to the AVIcontainer previously setup (block 286) for storage of images captured bythe video camera 198 (block 289). The computer control system 240controls the video camera 198 to capture images of the patient's tearfilm (block 289) until timeout or the user terminates image capture(block 290) and image capture halts or ends (block 291). Images capturedby the video camera 198 and provided to the computer control system 240over the USB port 283 are stored by the computer control system 240 inRAM 268.

The captured images of the patient's ocular tear film can subsequentlybe processed and analyzed to determine tear film characteristics of acontact lens wearer patient, as described in more detail below andthroughout the remainder of this disclosure. The process in thisembodiment involves processing tear film image pairs to performbackground subtraction, as previously discussed. For example, imagetiling may be performed to provide the tear film image pairs, ifdesired. The processing can include simply displaying the patient's tearfilm or determining tear film characteristics of a contact lens wearerpatient (block 293). If the display option is selected to allow atechnician to visually view the patient's tear film, display processingis performed (block 294) which can be the display processing 270described in more detail below with regard to FIG. 36. For example, thecomputer control system 240 can provide a combination of images of thepatient's tear film that show the entire region of interest of the tearfilm on the display 174. The displayed image may include the backgroundsignal or may have the background signal subtracted. If determining tearfilm characteristics of a contact lens wearer patient is desired, thecomputer control system 240 performs pre-processing of the tear filmimages for determining tear film characteristics of a contact lenswearer patient (block 295), which can be the pre-processing 260described in more detail below with regard to FIG. 28. The computercontrol system 240 also performs post-processing of the tear film imagesfor determining tear film characteristics of a contact lens wearerpatient (block 296), which can be the post-processing 262 described inmore detail below with regard to FIG. 28.

Pre-Processing

FIG. 19 illustrates an exemplary pre-processing system 260 forpre-processing ocular tear film images captured by the OSI device 170for eventual analysis and determining tear film characteristics of acontact lens wearer patient. In this system, the video camera 198 hasalready taken the first and second tiled images of a patient's oculartear film, as previously illustrated in FIGS. 11-13, and provided theimages to the video acquisition system 256. The frames of the first andsecond images were then loaded into RAM 258 by the video acquisitionsystem 256. Thereafter, as illustrated in FIG. 19, the computer controlsystem 240 commands the pre-processing system 260 to pre-process thefirst and second images. An exemplary GUI utility 280 is illustrated inFIG. 20 that may be employed by the computer control system 240 to allowa clinician to operate the OSI device 170 and control pre-processingsettings 264 and post-processing settings 266, which will be describedlater in this application. In this regard, the pre-processing system 260loads the first and second image frames of the ocular tear film from RAM258 (block 300). The exemplary GUI utility 280 in FIG. 19 allows for astored image file of previously stored video sequence of first andsecond image frames captured by the video camera 198 by entering a filename in the file name field 351. A browse button 352 also allowssearches of the memory for different video files, which can either bebuffered by selecting a buffered box 354 or loaded for pre-processing byselecting the load button 356.

If the loaded first and second image frames of the tear film arebuffered, they can be played using display selection buttons 358, whichwill in turn display the images on the display 174. The images can beplayed on the display 174 in a looping fashion, if desired, by selectingthe loop video selection box 360. A show subtracted video selection box370 in the GUI utility 280 allows a clinician to show the resulting,subtracted video images of the tear film on the display 174representative of the resulting signal comprised of the second outputsignal combined or subtracted from the first output signal, or viceversa. Also, by loading the first and second image frames, thepreviously described subtraction technique can be used to removebackground image from the interference signal representing interferenceof the specularly reflected light from the tear film, as previouslydescribed above and illustrated in FIG. 13 as an example. The firstimage is subtracted from the second image to subtract or remove thebackground signal in the portions producing specularly reflected lightin the second image, and vice versa, and then combined to produce aninterference interaction of the specularly reflected light of the entirearea or region of interest of the tear film, as previously illustratedin FIG. 13 (block 302 in FIG. 19). For example, this processing could beperformed using the Matlab® function “cvAbsDiff.”

The subtracted image containing the specularly reflected light from thetear film can also be overlaid on top of the original image capture ofthe tear film to display an image of the entire eye and the subtractedimage in the display 174 by selecting the show overlaid original videoselection box 362 in the GUI utility 280 of FIG. 20. An example of anoverlaid original video to the subtracted image of specularly reflectedlight from the tear film is illustrated in the image 363 of FIG. 21.This overlay is provided so that flashing images of specularly reflectedlight from the tear film are not displayed, which may be unpleasant tovisualize. The image 363 of the tear film illustrated in FIG. 21 wasobtained with a DBK 21AU04 Bayer VGA (640×480) video camera having aPentax VS-LD25 Daitron 25-mm fixed focal length lens with maximumaperture at a working distance of 120 mm and having the followingsettings, as an example:

Gamma=100 (to provide linearity with exposure value)

Exposure= 1/16 second

Frame rate=60 fps

Data Format=BY8

Video Format=-uncompressed, RGB 24-bit AVI

Hue=180 (neutral, no manipulation)

Saturation=128 (neutral, no manipulation)

Brightness=0 (neutral, no manipulation)

Gain=260 (minimum available setting in this camera driver)

White balance=B=78; R=20.

Thresholding

Any number of optional pre-processing steps and functions can next beperformed on the resulting combined tear film image(s), which will nowbe described. For example, an optional threshold pre-processing functionmay be applied to the resulting image or each image in a video of imagesof the tear film (e.g., FIG. 13) to eliminate pixels that have asubtraction difference signal below a threshold level (block 304 in FIG.19). Image threshold provides a black and white mask (on/off) that isapplied to the tear film image being processed to assist in removingresidual information that may not be significant enough to be analyzedand/or may contribute to inaccuracies in analysis of the tear film. Thethreshold value used may be provided as part of a threshold valuesetting provided by a clinician as part of the pre-processing settings264. For example, the GUI utility 280 in FIG. 20 includes a computethreshold selection box 372 that may be selected to performthresholding, where the threshold brightness level can be selected viathe threshold value slide 374. The combined tear film image or thecontact lens-based region of interest 127 of FIG. 13 is copied andconverted to grayscale. The grayscale image has a threshold appliedaccording to the threshold setting to obtain a binary (black/white)image that will be used to mask the combined tear film image of FIG. 13.After the mask is applied to the combined tear film image of FIG. 13,the new combined tear film image is stored in RAM 258. The areas of thetear film image that do not meet the threshold brightness level areconverted to black as a result of the threshold mask.

FIGS. 22A and 22B illustrate examples of threshold masks for thecombined tear film provided in FIG. 13. FIG. 22A illustrates a thresholdmask 320 for a threshold setting of 70 counts out of a full scale levelof 255 counts. FIG. 22B illustrates a threshold mask 322 for a thresholdsetting of 50. Note that the threshold mask 320 in FIG. 22A containsless portions of the combined tear film image, because the thresholdsetting is higher than for the threshold mask 322 of FIG. 22B. When thethreshold mask according to a threshold setting of 70 is applied to theexemplary combined tear film image of FIG. 13, the resulting tear filmimage is illustrated FIG. 23. Much of the residual subtracted backgroundimage that surrounds the area or region of interest has been maskedaway.

Erode and Dilate

Another optional pre-processing function that may be applied to theresulting image or each image in a video of images of the tear film tocorrect anomalies in the combined tear film image(s) is the erode anddilate functions (block 306 in FIG. 19). The erode function generallyremoves small anomaly artifacts by subtracting objects with a radiussmaller than an erode setting (which is typically in number of pixels)removing perimeter pixels where interference information may not be asdistinct or accurate. The erode function may be selected by a clinicianin the GUI utility 280 (see FIG. 20) by selecting the erode selectionbox 376. If selected, the number of pixels for erode can be provided inan erode pixels text box 378. Dilating generally connects areas that areseparated by spaces smaller than a minimum dilate size setting by addingpixels of the eroded pixel data values to the perimeter of each imageobject remaining after the erode function is applied. The dilatefunction may be selected by a clinician in the GUI utility 280 (see FIG.20) by providing the number of pixels for dilating in a dilate pixelstext box 380. Erode and dilate can be used to remove small regionanomalies in the resulting tear film image prior to analyzing theinterference interactions to reduce or avoid inaccuracies. Theinaccuracies may include those caused by bad pixels of the video camera198 or from dust that may get onto a scanned image, or more commonly,spurious specular reflections such as: tear film meniscus at thejuncture of the eyelids, glossy eyelash glints, wet skin tissue, etc.FIG. 24 illustrates the resulting tear film image of FIG. 23 after erodeand dilate functions have been applied and the resulting tear film imageis stored in RAM 258. As illustrated therein, pixels previously includedin the tear film image that were not in the tear film area or region ofinterest are removed. This prevents data in the image outside the areaor region of interest from affecting the analysis of the resulting tearfilm image(s).

Removing Blinks/Other Anomalies

Another optional pre-processing function that may be applied to theresulting image or each image in a video of images of the tear film tocorrect anomalies in the resulting tear film image is to remove framesfrom the resulting tear film image that include patient blinks orsignificant eye movements (block 308 in FIG. 19). As illustrated in FIG.19, blink detection is shown as being performed after a threshold anderode and dilate functions are performed on the tear film image or videoof images. Alternatively, the blink detection could be performedimmediately after background subtraction, such that if a blink isdetected in a given frame or frames, the image in such frame or framescan be discarded and not pre-processed. Not pre-processing images whereblinks are detected may increase the overall speed of pre-processing.The remove blinks or movement pre-processing may be selectable. Forexample, the GUI utility 280 in FIG. 20 includes a remove blinksselection box 384 to allow a user to control whether blinks and/or eyemovements are removed from a resulting image or frames of the patient'stear film prior to analysis. Blinking of the eyelids covers the oculartear film, and thus does not produce interference signals representingspecularly reflected light from the tear film. If frames containingwhole or partial blinks obscuring the area or region of interest in thepatient's tear film are not removed, it would introduce errors in theanalysis of the interference signals to determine characteristics of thepatient's ocular tear film involving contact lens wear. Further, framesor data with significant eye movement between sequential images orframes can be removed during the detect blink pre-processing function.Large eye movements could cause inaccuracy in analysis of a patient'stear film or any area of interest when employing subtraction techniquesto remove background signal, because subtraction involves subtractingframe-pairs in an image that closely match spatially. Thus, if there issignificant eye movement between first and second images that are to besubtracted, frame pairs may not be closely matched spatially thusinaccurately removing background signal, and possibly removing a portionof the interference image of specularly reflected light from the tearfilm.

Different techniques can be used to determine blinks in an ocular tearfilm image and remove the frames as a result. For example, in oneembodiment, the computer control system 240 directs the pre-processingsystem 260 to review the stored frames of the resulting images of thetear film to monitor for the presence of an eye pupil using patternrecognition. A Hough Circle Transform may be used to detect the presenceof the eye pupil in a given image or frame. If the eye pupil is notdetected, it is assembled such that the image or frame contains an eyeblink and thus should be removed or ignored during pre-processing fromthe resulting image or video of images of the tear film. The resultingimage or video of images can be stored in RAM 258 for subsequentprocessing and/or analysis.

In this regard, in one embodiment, detecting eye blinks in an oculartear film image or frame by detecting the pupil and removing desiredblink frames that do not contain an image of the pupil as a result maybe performed as follows. First, ocular tear film frame pairs, onecontaining specularly reflected light and background signal (i.e., frame1), and the other containing background signal (i.e., frame 2) are addedtogether to provide a resultant image (i.e., frame 1+[frame 2−frame 1]).A grayscale is created of the resultant image, for example using a8-bit, 255 value scale. Providing a grayscale of the resultant imageallows enhanced identification of darker pixels as opposed to lighterpixels, to try to identify pixels associated with the pupil, as anon-limiting example. As discussed above, determining that a pupil is inan ocular tear film image is one direct indication of whether the oculartear film frame contains a partial or full eye blink. Thereafter in thisexample, the darkest pixel in resultant grayscale frame is found. Then,all pixels within a given intensity count are found (e.g., within 7).These are the darkest areas of the frame and include the pupil. A binaryresultant frame is then created with resultant grayscale frame totransform the darker pixels to white color. That binary resultant frameis then eroded and dilated (similar to as discussed in other examplesherein for tear film measurement purposes) using a sample disk. Thelarger or largest contiguous pixels having white color is found in theresultant binary frame. A check is next made to make sure that larger orlargest contiguous pixels having white color contains at least a desiredminimum number of pixels (e.g., 3000) and has a desired eccentricity(e.g., 0.8 or lower). If so, this larger or largest contiguous pixelshaving white color is deemed to be the pupil. If previous frame from thecurrent frame was also deemed to contain the pupil by ensuring thecentroid of the larger or largest contiguous pixels did not shift bymore than a designated number of pixels (e.g., 50 pixels), then thecurrent frame is deemed to contain the pupil and is not rejected. If thecurrent frame is not deemed to contain the pupil, the frame can berejected.

In another embodiment, blinks and significant eye movements are detectedusing a histogram sum of the intensity of pixels in a resultingsubtracted image or frame of a first and second image of the tear film.The resulting or subtracted image can be converted to grayscale (i.e.,255 levels) and a histogram generated with the gray levels of thepixels. The total of all the histogram bins are summed. In the case oftwo identical frames that are subtracted, the histogram sum would bezero. However, even without an eye blink or significant eye movement,two sequentially captured frames of the patient's eye and theinterference signals representing the specularly reflected light fromthe tear film are not identical. However, frame pairs with littlemovement will have a low histogram sum, while frame pairs with greatermovement will yield a larger histogram sum. If the histogram sum isbeyond a pre-determined threshold, an eye blink or large eye movementcan be assumed and the image or frame removed. For example, the GUIutility 280 illustrated in FIG. 20 includes a histogram sum slide bar386 that allows a user to set the threshold histogram sum. The thresholdhistogram sum for determining whether a blink or large eye movementshould be assumed and thus the image removes from analysis of thepatient's tear film can be determined experimentally, or adaptively overthe course of a frame playback, assuming that blinks occur at regularintervals.

An advantage of a histogram sum of intensity method to detect eye blinksor significant eye movements is that the calculations are highlyoptimized as opposed to pixel-by-pixel analysis, thus assisting withreal-time processing capability. Further, there is no need to understandthe image structure of the patient's eye, such as the pupil or the irisdetails. Further, the method can detect both blinks and eye movements.

In this regard, in one embodiment, detecting eye blinks in an oculartear film image or frame based on an intensity method may be performedas follows. First, the ocular tear film frame pairs, one containingspecularly reflected light and background signal (i.e., frame 1), andthe other containing background signal (i.e., frame 2) are subtractedfrom each together to provide a resultant image (i.e., [frame 2−frame1]). A grayscale is created of the resultant image (e.g., 8-bits, 255sample levels). A histogram is then calculated for the resultantgrayscale image by, for example, dividing intensity in the resultantgrayscale image into a desired number of bins (e.g., 64 bins of 4 countseach). The height of the tallest bin is set to a defined level (e.g.,200) and the scale of all other bins adjusted accordingly. All scaledbins are summed and compared to a predefined limit (e.g., 1000). Ifhistogram sum is greater than this predefined limit, the resultant frameis rejected as a frame having a blink.

To remove blink islands, trains or sequences of consecutive non-blinkframes bookended by blink frames can be identified. If a train consistsof three or fewer non-blink frames, those frames can be rejected asblink frames. The centroid of each resultant subtracted frame iscalculated to find the location of each non-blink pixel (e.g., find theaverage location in X-Y coordinates of center of non-blink pixel). Abounding box of each resultant subtracted frame is also calculated. Theaverage centroid location is calculated for all non-blink frames. Theaverage bounding box location is calculated for all non-blink frames. Ifthe centroid for a given frame deviates from the average centroidlocation for all frames by more than a defined number of pixels (e.g.,30) up, down, or temporally (from temple or nose of patient), then thatframe can be rejected as a blink frame. If top, bottom, or temporaledges of bounding box deviate from the average bounding box location bymore than 30 pixels, the frame can be rejected as a blink frame. Theblink island removal process can be repeated labeling blink islands aseither blink or non-blink islands. Optionally, a first number of frames(e.g., 5) after each blink to allow tear film to stabilize beforequantifying lipid layer thickness.

Another alternate technique to detect blinks in the tear film image orvideo of images for possible removal is to calculate a simple averagegray level in an image or video of images. Because the subtracted,resulting images of the tear film subtract background signal, and havebeen processed using a threshold mask, and erode and dilate functionsperformed in this example, the resulting images will have a loweraverage gray level due to black areas present than if a blink ispresent. A blink contains skin color, which will increase the averagegray level of an image containing a blink. A threshold average graylevel setting can be provided. If the average gray level of a particularframe is below the threshold, the frame is ignored from further analysisor removed from the resulting video of frames of the tear film.

Another alternate technique to detect blinks in an image or video ofimages for removal is to calculate the average number of pixels in agiven frame that have a gray level value below a threshold gray levelvalue. If the percentage of pixels in a given frame is below a definedthreshold percentage, this can be an indication that a blink hasoccurred in the frame, or that the frame is otherwise unworthy ofconsideration when analyzing the tear film. Alternatively, a spatialfrequency calculation can be performed on a frame to determine theamount of fine detail in a given frame. If the detail present is below athreshold detail level, this may be an indication of a blink or otherobscurity of the tear film, since skin from the eyelid coming down andbeing captured in a frame will have less detail than the subtractedimage of the tear film. A histogram can be used to record any of theabove-referenced calculations to use in analyzing whether a given frameshould be removed from the final pre-processed resulting image or imagesof the tear film for analysis.

ICC Profiling

Pre-processing of the resulting tear film image(s) may also optionallyinclude applying an International Colour Consortium (ICC) profile to thepre-processed interference images of the tear film (block 310, FIG. 19).FIG. 25 illustrates an optional process of loading an ICC profile intoan ICC profile 331 in the computer control system 240 (block 330). Inthis regard, the GUI utility 280 illustrated in FIG. 20 also includes anapply ICC box 392 that can be selected by a clinician to load the ICCprofile 331. The ICC profile 331 may be stored in memory in the computercontrol system 240, including in RAM 258. In this manner, the GUIutility 280 in FIG. 20 also allows for a particular ICC profile 331 tobe selected for application in the ICC profile file text box 394. TheICC profile 331 can be used to adjust color reproduction from scannedimages from cameras or other devices into a standard red-green-blue(RGB) color space (among other selectable standard color spaces) definedby the ICC and based on a measurement system defined internationally bythe Commission Internationale de l′Eclairage (CIE). Adjusting thepre-processed resulting tear film interference images corrects forvariations in the camera color response and the light source spectrumand allows the images to be compatibly compared with a tear film layerinterference model to measure the thickness of a TFLT, as will bedescribed later in this application. The tear film layers represented inthe tear film layer interference model can be LLTs, ALTs, or both, aswill be described in more detail below.

In this regard, the ICC profile 331 may have been previously loaded tothe OSI device 170 before imaging of a patient's tear film and alsoapplied to a tear film layer interference model when loaded into the OSIdevice 170 independent of imaging operations and flow. As will bediscussed in more detail below, a tear film layer interference model inthe form of a TFLT palette 333 containing color values representinginterference interactions from specularly reflected light from a tearfilm for various LLTs and ALTs can also be loaded into the OSI device170 (block 332 in FIG. 25). The tear film layer interference model 333contains a series of color values that are assigned LLTs and/or ALTsbased on a theoretical tear film layer interference model to be comparedagainst the color value representations of interference interactions inthe resulting image(s) of the patient's tear film. When applying theoptional ICC profile 331 to the tear film layer interference model 333(block 334 in FIG. 25), the color values in both the tear film layerinterference model and the color values representing interferenceinteractions in the resulting image of the tear film are adjusted for amore accurate comparison between the two to measure LLT and/or ALT.

Brightness

Also as an optional pre-processing step, brightness and red-green-blue(RGB) subtract functions may be applied to the resulting interferencesignals of the patient's tear film before post-processing for analysisand measuring TFLT is performed (blocks 312 and 314 in FIG. 19). Thebrightness may be adjusted pixel-by-pixel by selecting the adjustbrightness selection box 404 according to a corresponding brightnesslevel value provided in a brightness value box 406, as illustrated inthe GUI utility 280 of FIG. 20. When the brightness value box 406 isselected, the brightness of each palette value of the tear filminterference model 333 is also adjusted accordingly.

RGB Subtraction (Normalization)

The RGB subtract function subtracts a DC offset from the interferencesignal in the resulting image(s) of the tear film representing theinterference interactions in the interference signal. An RGB subtractsetting may be provided from the pre-processing settings 264 to apply tothe interference signal in the resulting image of the tear film tonormalize against. As an example, the GUI utility 280 in FIG. 20 allowsan RGB offset to be supplied by a clinician or other technician for usein the RGB subtract function. As illustrated therein, the subtract RGBfunction can be activated by selecting the RGB subtract selection box396. If selected, the individual RGB offsets can be provided in offsetvalue input boxes 398. After pre-processing is performed, if any, on theresulting image, the resulting image can be provided to apost-processing system to measure TFLT (block 316 in FIG. 19), asdiscussed later below in this application.

Displaying Images

The resulting images of the tear film may also be displayed on thedisplay 174 of the OSI device 170 for human diagnosis of the patient'socular tear film. The OSI device 170 is configured so that a cliniciancan display and see the raw captured image of the patient's eye 192 bythe video camera 198, the resulting images of the tear film beforepre-processing, or the resulting images of the tear film afterpre-processing. Displaying images of the tear film on the display 174may entail different settings and steps. For example, if the videocamera 198 provides linear images of the patient's tear film, the linearimages must be converted into a non-linear format to be properlydisplayed on the display 174. In this regard, a process that isperformed by the visualization system 270 according to one embodiment isillustrated in FIG. 26.

As illustrated in FIG. 26, the video camera 198 has already taken thefirst and second tiled images of a patient's ocular tear film aspreviously illustrated in FIGS. 11-13, and provided the images to thevideo acquisition system 256. The frames of the first and second imageswere then loaded into RAM 258 by the video acquisition system 256.Thereafter, as illustrated in FIG. 26, the computer control system 240commands the visualization system 270 to process the first and secondimages to prepare them for being displayed on the display 174, 338. Inthis regard, the visualization system 270 loads the first and secondimage frames of the ocular tear film from RAM 258 (block 335). Thepreviously described subtraction technique is used to remove backgroundsignal from the interference interactions of the specularly reflectedlight from the tear film, as previously described above and illustratedin FIG. 13. The first image(s) is subtracted from the second image(s) toremove background signal in the illuminated portions of the firstimage(s), and vice versa, and the subtracted images are then combined toproduce an interference interaction of the specularly reflected light ofthe entire area or region of interest of the tear film, as previouslydiscussed and illustrated in FIG. 13 (block 336 in FIG. 26).

Again, for example, this processing could be performed using the Matlab®function “cvAbsDiff.” Before being displayed, the contrast andsaturation levels for the resulting images can be adjusted according tocontrast and saturation settings provided by a clinician via the userinterface system 278 and/or programmed into the visualization system 270(block 337). For example, the GUI utility 280 in FIG. 20 provides anapply contrast button 364 and a contrast setting slide 366 to allow theclinician to set the contrast setting in the display settings 274 fordisplay of images on the display 174. The GUI utility 280 also providesan apply saturation button 368 and a saturation setting slide 369 toallow a clinician to set the saturation setting in the display settings274 for the display of images on the display 174. The images can then beprovided by the visualization system 270 to the display 174 fordisplaying (block 338 in FIG. 26). Also, any of the resulting imagesafter pre-processing steps in the pre-processing system 260 can beprovided to the display 174 for processing.

FIGS. 27A-27C illustrate examples of different tear film images that aredisplayed on the display 174 of the OSI device 170. FIG. 27A illustratesa first image 339 of the patient's tear film showing the tiled patterncaptured by the video camera 198. This image is the same image asillustrated in FIG. 11 and previously described above, but processedfrom a linear output from the video camera 198 to be properly displayedon the display 174. FIG. 27B illustrates a second image 340 of thepatient's tear film illustrated in FIG. 12 and previously describedabove. FIG. 27C illustrates a resulting “overlaid” image 341 of thefirst and second images 339, 340 of the patient's tear film and toprovide interference interactions of the specularly reflected light fromthe tear film over the entire area or region of interest. This is thesame image as illustrated in FIG. 13 and previously described above.

In this example, the original number of frames of the patient's tearfilm captured can be reduced by half due to the combination of the firstand second tiled pattern image(s). Further, if frames in the subtractedimage frames capture blinks or erratic movements, and these frames areeliminated in pre-processing, a further reduction in frames will occurduring pre-processing from the number of images raw captured in imagesof the patient's tear film. Although these frames are eliminated frombeing further processed, they can be retained for visualizationrendering a realistic and natural video playback. Further, by applying athresholding function and erode and dilating functions, the number ofnon-black pixels which contain TFLT interference information issubstantially reduced as well. Thus, the amount of pixel informationthat is processed by the post-processing system 262 is reduced, and maybe on the order of 70% less information to process than the raw imagecapture information, thereby pre-filtering for the desired interferenceROI and reducing or elimination potentially erroneous information aswell as allowing for faster analysis due to the reduction ininformation.

At this point, the resulting images of the tear film have beenpre-processed by the pre-processing system 260 according to whateverpre-processing settings 264 and pre-processing steps have been selectedor implemented by the computer control system 240. The resulting imagesof the tear film are ready to be processed for determining tear filmcharacteristics of a contact lens wearer patient, including the processdescribed above in FIG. 6 and other exemplary processes described below.An embodiment of the post-processing performed by the post-processingsystem 262 is illustrated in the flowchart of FIG. 28.

Tear Film Interference Models

As illustrated in FIG. 28, pre-processed images 343 of the resultingimages of the tear film are retrieved from RAM 258 where they werepreviously stored by the pre-processing system 260. Before discussingthe particular embodiment of the post-processing system 262 in FIG. 28,in general, to determining tear film characteristics of a contact lenswearer patient, the RGB color values of the pixels in the resultingimages of the tear film are compared against color values stored in alipid layer-contact lens layer interference model that has beenpreviously loaded into the OSI device 170 (see FIG. 25). The lipidlayer-contact lens layer interference model is based on a tear filminterference model, but altered with an index of refraction of anexpected or specific contact lens used in place of the aqueous layer.The lipid layer-contact lens layer interference model and/or a tear filminterference model may be stored as a TFLT palette 333 containing RGBvalues representing interference colors for given LLTs and/or ALTs. TheTFLT palette contains interference color values that represent TFLTsbased on a theoretical tear film interference model in this embodiment.Depending on the TFLT palette provided, the interference color valuesrepresented therein may represent LLTs, ALTs, or both. An estimation ofTFLT for each ROI pixel is based on this comparison. This estimate ofTFLT is then provided to the clinician via the display 174 and/orrecorded in memory to assist in diagnosing DES.

Before discussing embodiments of how the TFLTs as one type of tear filmcharacteristic are estimated from the pre-processed resulting imagecolored interference interactions resulting from specularly reflectedlight from the tear film, tear film interference modeling is firstdiscussed. Tear film interference modeling can be used to determine aninterference color value for a given TFLT to measure TFLT, which caninclude both LLT and/or ALT.

Although the interference signals representing specularly reflectedlight from the tear film are influenced by all layers in the tear film,the analysis of interference interactions due to the specularlyreflected light can be analyzed under a 2-wave tear film model (i.e.,two reflections) to measure LLT. A 2-wave tear film model is based on afirst light wave(s) specularly reflecting from the air-to-lipid layertransition of a tear film and a second light wave specularly reflectingfrom the lipid layer-to-aqueous layer transition of the tear film. Inthe 2-wave model, the aqueous layer is effective ignored and treated tobe of infinite thickness. To measure LLT using a 2-wave model, a 2-wavetear film model was developed wherein the light source and lipid layersof varying thicknesses were modeled mathematically. To model thetear-film interference portion, commercially available software, such asthat available by FilmStar and Zemax as examples, allows imagesimulation of thin films for modeling. Relevant effects that can beconsidered in the simulation include refraction, reflection, phasedifference, polarization, angle of incidence, and refractive indexwavelength dispersion. For example, a lipid layer could be modeled ashaving an index of refraction of 1.48 or as a fused silica substrate(SiO₂) having a 1.46 index of refraction. A back material, such asMagnesium Flouride (MgF₂) having an index of refraction of 1.38 may beused to provide a 2-wave model of air/SiO₂/MgF₂ (1.0/1.46/1.38) for atear film interference model or the index of refraction of a contactlens in place of 1.38. To obtain more accurate modeling results, themodel can include the refractive index and wavelength dispersion valuesof biological lipid material and biological aqueous material, found fromthe literature, thus to provide a precise two-wave model ofair/lipid/aqueous layers. Thus, a 2-wave tear film interference modelallows measurement of LLT regardless of ALT.

Simulations can be mathematically performed by varying the LLT between10 to 300 nm. As a second step, the RGB color values of the resultinginterference signals from the modeled light source causing the modeledlipid layer to specularly reflected light and received by the modeledcamera were determined for each of the modeled LLT. These RGB colorvalues representing interference interactions in specularly reflectedlight from the modeled tear film were used to form a 2-wave model LLTpalette, wherein each RGB color value is assigned a different LLT. Theresulting subtracted image of the first and second images from thepatient's tear film containing interference signals representingspecularly reflected light are compared to the RGB color values in the2-wave model LLT palette to measure LLT.

In another embodiment, a 3-wave tear film interference model may beemployed to estimate LLT. A 3-wave tear film interference model does notassume that the aqueous layer is infinite in thickness. In an actualpatient's tear film, the aqueous layer is not infinite. The 3-wave tearfilm interference model is based on both the first and second reflectedlight waves of the 2-wave model and additionally light wave(s)specularly reflecting from the aqueous-to-mucin layer and/or corneatransitions. Thus, a 3-wave tear film interference model recognizes thecontribution of specularly reflected light from the aqueous-to-mucinlayer and/or cornea transition that the 2-wave tear film interferencemodel does not. To estimate LLT using a 3-wave tear film interferencemodel, a 3-wave tear film model was previously constructed wherein thelight source and a tear film of varying lipid and aqueous layerthicknesses were mathematically modeled. For example, a lipid layercould be mathematically modeled as a material having an index ofrefraction of 1.48 or as fused silica substrate (SiO₂), which has a 1.46index of refraction. Different thicknesses of the lipid layer can besimulated. A fixed thickness aqueous layer (e.g., >=2 μm) could bemathematically modeled as Magnesium Flouride (MgF₂) having an index ofrefraction of 1.38, or for a lipid layer-contact lens layer interferencemodel, an index of refraction for a contact lens. A biological corneacould be mathematically modeled as fused silica with no dispersion,thereby resulting in a 3-wave model of air/SiO₂/MgF₂/SiO₂ (i.e.,1.0/1.46/1.38/1.46 with no dispersion). As before, accurate results areobtained if the model can include the refractive index and wavelengthdispersion values of biological lipid material, biological aqueousmaterial, and cornea tissue, found from the literature, thus to providea precise two-wave model of air/lipid/aqueous/cornea layers. Theresulting interference interactions of specularly reflected light fromthe various LLT values and with a fixed ALT value are recorded in themodel and, when combined with modeling of the light source and thecamera, will be used to compare against interference from specularlyreflected light from an actual tear film to measure LLT and/or ALT.

In another embodiment of the OSI device 170 and the post-processingsystem 262 in particular, a 3-wave tear film interference model isemployed to estimate both LLT and ALT. In this regard, instead ofproviding either a 2-wave theoretical tear film interference model thatassumes an infinite aqueous layer thickness or a 3-wave model thatassumes a fixed or minimum aqueous layer thickness (e.g., ≧2 μm), a3-wave theoretical tear film interference model is developed thatprovides variances in both LLT and ALT in the mathematical model of thetear film. Again, the lipid layer in the tear film model could bemodeled mathematically as a material having an index of refraction of1.48 or as fused silica substrate (SiO₂) having a 1.46 index ofrefraction. The aqueous layer could be modeled mathematically asMagnesium Flouride (MgF₂) having an index of refraction of 1.38, or anindex of refraction of a contact lens for a lipid layer-contact lenslayer interference model. A biological cornea could be modeled as fusedsilica with no dispersion, thereby resulting in a 3-wave model ofair/SiO₂/MgF₂/SiO₂ (no dispersion). Once again, the most accurateresults are obtained if the model can include the refractive index andwavelength dispersion values of biological lipid material, biologicalaqueous material, and cornea tissue, found from the literature, thus toprovide a precise two-wave model of air/lipid/aqueous/cornea layers.Thus, a two-dimensional (2D) TFLT palette 430 (FIG. 29A) is produced foranalysis of interference interactions from specularly reflected lightfrom the tear film. One dimension of the TFLT palette 430 represents arange of RGB color values each representing a given theoretical LLTcalculated by mathematically modeling the light source and the cameraand calculating the interference interactions from specularly reflectedlight from the tear film model for each variation in LLT 434 in the tearfilm interference model. A second dimension of the TFLT palette 430represents ALT also calculated by mathematically modeling the lightsource and the camera and calculating the interference interactions fromspecularly reflected light from the tear film interference model foreach variation in ALT 432 at each LLT value 434 in the tear filminterference model.

Post-Processing/TFLT Measurement

To measure TFLT, a spectral analysis of the resulting interferencesignal or image is performed during post-processing to calculate a TFLT.In one embodiment, the spectral analysis is performed by performing alook-up in a tear film interference model to compare one or moreinterference interactions present in the resulting interference signalrepresenting specularly reflected light from the tear film to the RGBcolor values in the tear film interference model. In this regard, FIGS.29A and 29B illustrate two examples of palette models for use inpost-processing of the resulting image having interference interactionsfrom specularly reflected light from the tear film using a 3-wavetheoretical tear film interference model developed using a 3-wavetheoretical tear film model, but such could also be used as atheoretical lipid layer-contact lens layer model if adjusted using anindex of refraction of a contact lens. In general, an RGB numericalvalue color scheme is employed in this embodiment, wherein the RGB valueof a given pixel from a resulting pre-processed tear film image of apatient is compared to RGB values in the 3-wave tear film interferencemodel representing color values for various LLTs and ALTs in a 3-wavemodeled theoretical tear film. The closest matching RGB color is used todetermine the LLT and/or ALT for each pixel in the resulting signal orimage. All pixels for a given resulting frame containing the resultinginterference signal are analyzed in the same manner on a pixel-by-pixelbasis. A histogram of the LLT and ALT occurrences is then developed forall pixels for all frames and the average LLT and ALT determined fromthe histogram (block 348 in FIG. 28).

FIG. 29A illustrates an exemplary TFLT palette 430 in the form of colorsrepresenting the included RGB color values representing interference ofspecularly reflected light from a 3-wave theoretical tear film modelused to compared colors from the resulting image of the patient's tearfilm to estimate LLT and ALT. FIG. 29B illustrates an alternativeexample of a TFLT palette 430′ in the form of colors representing theincluded RGB color values representing interference of specularlyreflected light from a 3-wave theoretical tear film model used tocompare colors from the resulting image of the patient's tear film toestimate LLT and ALT. As illustrated in FIG. 29A, the TFLT palette 430contains a plurality of hue colors arranged in a series of rows 432 andcolumns 434. In this example, there are 144 color hue entries in thepalette 430, with nine (9) different ALTs and sixteen (16) differentLLTs in the illustrated TFLT palette 430, although another embodimentincludes thirty (30) different LLTs. Providing any number of LLT andTFLT increments is theoretically possible. The columns 434 in the TFLTpalette 430 contain a series of LLTs in ascending order of thicknessfrom left to right. The rows 432 in the TFLT palette 430 contain aseries of ALTs in ascending order of thickness from top to bottom. Thesixteen (16) LLT increments provided in the columns 434 in the TFLTpalette 430 are 25, 50, 75, 80, 90, 100, 113, 125, 138, 150, 163, 175,180, 190, 200, and 225 nanometers (nm). The nine (9) ALT incrementsprovided in the rows 432 in the TFLT palette 430 are 0.25, 0.5, 0.75,1.0, 1.25, 1.5, 1.75, 3.0 and 6.0 μm. As another example, as illustratedin FIG. 29B, the LLTs in the columns 434′ in the TFLT palette 430′ areprovided in increments of 10 nm between 0 nm and 160 nm. The nine (9)ALT increments provided in the rows 432′ in the TFLT palette 430 are0.3, 0.5, 0.08, 1.0, 1.3, 1.5, 1.8, 2.0 and 5.0 μm.

As part of a per pixel LLT analysis 344 provided in the post-processingsystem 262 in FIG. 28, for each pixel in each of the pre-processedresulting images of the area or region of interest in the tear film, aclosest match determination is made between the RGB color of the pixelto the nearest RGB color in the TFLT palette 430 (block 345 in FIG. 28).The ALTs and LLTs for that pixel are determined by the corresponding ALTthickness in the y-axis of the TFLT palette 430, and the correspondingLLT thickness in the x-axis of the TFLT palette 430. As illustrated inFIGS. 29A and 29B, the TFLT palette 430 colors are actually representedby RGB values. The pixels in each of the pre-processed resulting imagesof the tear film are also converted and stored as RGB values, althoughany other color representation can be used as desired, as long as thepalette and the image pixel data use the same representational colorspace. FIG. 30 illustrates the TFLT palette 430 in color pattern formwith normalization applied to each red-green-blue (RGB) color valueindividually. Normalizing a TFLT palette is optional. The TFLT palette430 in FIG. 30 is displayed using brightness control (i.e.,normalization, as previously described) and without the RGB valuesincluded, which may be more visually pleasing to a clinician ifdisplayed on the display 174. The GUI utility 280 allows selection ofdifferent palettes by selecting a file in the palette file drop down402, as illustrated in FIG. 20, each palette being specific to thechoice of 2-wave vs. 3-wave mode, the chosen source's spectrum, and thechosen camera's RGB spectral responses. To determine the closest pixelcolor in the TFLT palette 430, a Euclidean distance color differenceequation is employed to calculate the distance in color between the RGBvalue of a pixel from the pre-processed resulting image of the patient'stear film and RGB values in the TFLT palette 430 as follows below,although the present invention is not so limited:

Diff.=√((Rpixel−Rpalette)²⁺(Gpixel−Gpalette)²⁺(Bpixel−Bpalette)²)

Thus, the color difference is calculated for all palette entries in theTFLT palette 430. The corresponding LLT and ALT values are determinedfrom the color hue in the TFLT palette 430 having the least differencefrom each pixel in each frame of the pre-processed resulting images ofthe tear film. The results can be stored in RAM 258 or any otherconvenient storage medium. To prevent pixels without a close match to acolor in the TFLT palette 430 from being included in a processed resultof LLT and ALT, a setting can be made to discard pixels from the resultsif the distance between the color of a given pixel is not within theentered acceptable distance of a color value in the TFLT palette 430(block 346 in FIG. 28).

Each LLT and ALT determined for each pixel from a comparison in the TFLTpalette 430 via the closest matching color that is within a givendistance (if that post-proces sing setting 266 is set) or for all LLTand ALT determined values are then used to build a TFLT histogram. TheTFLT histogram is used to determine a weighted average of the LLT andALT values for each pixel in the resulting image(s) of the patient'stear film to provide an overall estimate of the patient's LLT and ALT.FIG. 31 illustrates an example of such a TFLT histogram 460. This TFLThistogram 440 may be displayed as a result of the shown LLT histogramselection box 400 being selected in the GUI utility 280 of FIG. 20. Asillustrated therein, for each pixel within an acceptable distance, theTFLT histogram 440 is built in a stacked fashion with determined ALTvalues 444 stacked for each determined LLT value 442 (block 349 in FIG.28). Thus, the TFLT histogram 440 represents LLT and ALT values for eachpixel. A horizontal line separates each stacked ALT value 444 withineach LLT bar.

One convenient way to determine the final LLT and ALT estimates is witha simple weighted average of the LLT and ALT values 442, 444 in the TFLThistogram 440. In the example of the TFLT histogram 440 in FIG. 31, theaverage LLT value 446 was determined to be 90.9 nm. The number ofsamples 448 (i.e., pixels) included in the TFLT histogram 440 was31,119. The frame number 450 indicates which frame of the resultingvideo image is being processed, since the TFLT histogram 440 representsa single frame result, or the first of a frame pair in the case ofbackground subtraction. The maximum distance 452 between the color ofany given pixel among the 31,119 pixels and a color in the TFLT palette430 was 19.9, 20 may have been the set limit (Maximum Acceptable PaletteDistance) for inclusion of any matches. The average distance 454 betweenthe color of each of the 31,119 pixels and its matching color in theTFLT palette 430 was 7.8. The maximum distance 452 and average distance454 values provide an indication of how well the color values of thepixels in the interference signal of the specularly reflected light fromthe patient's tear film match the color values in the TFLT palette 430.The smaller the distance, the closer the matches. The TFLT histogram 440can be displayed on the display 174 to allow a clinician to review thisinformation graphically as well as numerically. If either the maximumdistance 452 or average distance 454 values are too high, this may be anindication that the measured LLT and ALT values may be inaccurate, orthat the image normalization is not of the correct value. Furtherimaging of the patient's eye and tear film, or system recalibration canbe performed to attempt to improve the results. Also, a histogram 456 ofthe LLT distances 458 between the pixels and the colors in the TFLTpalette 430 can be displayed as illustrated in FIG. 32 to show thedistribution of the distance differences to further assist a clinicianin judgment of the results.

Other results can be displayed on the display 174 of the OSI device 170that may be used by a physician or technician to judge the LLT and/orALT measurement results. For example, FIG. 33 illustrates a thresholdwindow 424 illustrating a (inverse) threshold mask 426 that was usedduring pre-processing of the tear film images. In this example, thethreshold window 424 was generated as a result of the show thresholdwindow selection box 382 being selected in the GUI utility 280 of FIG.20. This may be used by a clinician to humanly evaluate whether thethreshold mask looks abnormal. If so, this may have caused the LLT andALT estimates to be inaccurate and may cause the clinician to discardthe results and image the patient's tear film again. The maximumdistance between the color of any given pixel among the 31,119 pixelsand a color in the palette 430 was 19.9 in this example.

FIG. 34 illustrates another histogram that may be displayed on thedisplay 174 and may be useful to a clinician. As illustrated therein, athree-dimensional (3D) histogram plot 460 is illustrated. The 3Dhistogram plot 460 is simply another way to graphically display the fitof the processed pixels from the pre-processed images of the tear filmto the TFLT palette 430. The plane defined by the LLT 462 and ALT 464axes represents the TFLT palette 430. The axis labeled “Samples” 466 isthe number of pixels that match a particular color in the TFLT palette430.

FIG. 35 illustrates a result image 428 of the specularly reflected lightfrom a patient's tear film. However, the actual pixel value for a givenarea on the tear film is replaced with the determined closest matchingcolor value representation in the TFLT palette 430 to a given pixel forthat pixel location in the resulting image of the patient's tear film(block 347 in FIG. 28). Visually displaying interference interactionsrepresenting the closest matching color value to the interferenceinteractions in the interference signal of the specularly reflectedlight from a patient's tear film in this manner may be helpful todetermine how closely the tear film interference model matches theactual color value representing the resulting image (or pixels in theimage).

Ambiguities can arise when calculating the nearest distance between anRGB value of a pixel from a tear film image and RGB values in a TFLTpalette, such as TFLT palettes 430 and 430′ in FIGS. 29A and 29B asexamples. This is because when the theoretical LLT of the TFLT paletteis plotted in RGB space for a given ALT in three-dimensional (3D) space,the TFLT palette 469 is a locus that resembles a pretzel like curve, asillustrated with a 2-D representation in the exemplary TFLT palettelocus 470 in FIG. 36. Ambiguities can arise when a tear film image RGBpixel value has close matches to the TFLT palette locus 470 atsignificantly different LLT levels. For example, as illustrated in theTFLT palette locus 470 in FIG. 36, there are three (3) areas of closeintersection 472, 474, 476 between RGB values in the TFLT palette locus470 even though these areas of close intersection 472, 474, 476represent substantially different LLTs on the TFLT palette locus 470.This is due to the cyclical phenomenon caused by increasing orders ofoptical wave interference, and in particular, first order versus secondorder interference for the LLT range in the tear films. Thus, if an RGBvalue of a tear film image pixel is sufficiently close to two differentLLT points in the TFLT palette locus 470, the closest RGB match may bedifficult to match. The closest RGB match may be to an incorrect LLT inthe TFLT palette locus 470 due to error in the camera and translation ofreceived light to RGB values. Thus, it may be desired to provide furtherprocessing when determining the closest RGB value in the TFLT palettelocus 470 to RGB values of tear film image pixel values when measuringTFLT.

In this regard, there are several possibilities that can be employed toavoid ambiguous RGB matches in a TFLT palette. For example, the maximumLLT values in a TFLT palette may be limited. For example, the TFLTpalette locus 470 in FIG. 36 includes LLTs between 10 nm and 300 nm. Ifthe TFLT palette locus 470 was limited in LLT range, such as 240 nm asillustrated in the TFLT palette locus 478 in FIG. 37, two areas of closeintersection 474 and 476 in the TFLT palette 469 in FIG. 36 are avoidedin the TFLT palette 469 of FIG. 37. This restriction of the LLT rangesmay be acceptable based on clinical experience since most patients donot exhibit tear film colors above the 240 nm range and dry eye symptomsare more problematic at thinner LLTs. In this scenario, the limited TFLTpalette 469 of FIG. 37 would be used as the TFLT palette in thepost-processing system 262 in FIG. 28, as an example.

Even by eliminating two areas of close intersection 474, 476 in the TFLTpalette 469, as illustrated in FIG. 37, the area of close intersection472 still remains in the TFLT palette locus 478. In this embodiment, thearea of close intersection 472 is for LLT values near 20 nm versus 180nm. In these regions, the maximum distance allowed for a valid RGB matchis restricted to a value of about half the distance of the TFLTpalette's 469 nearing ambiguity distance. In this regard, RGB values fortear film pixels with match distances exceeding the specified values canbe further excluded from the TFLT calculation to avoid tear film pixelshaving ambiguous corresponding LLT values for a given RGB value to avoiderror in TFLT measurement as a result.

In this regard, FIG. 38 illustrates the TFLT palette locus 478 in FIG.37, but with a circle of radius R swept along the path of the TFLTpalette locus 478 in a cylinder or pipe 480 of radius R. Radius R is theacceptable distance to palette (ADP), which can be configured in thecomputer control system 240. When visualized as a swept volume insidethe cylinder or pipe 480, RGB values of tear film image pixels that fallwithin those intersecting volumes may be considered ambiguous and thusnot used in calculating TFLT, including the average TFLT. The smallerthe ADP is set, the more poorly matching tear film image pixels that maybe excluded in TFLT measurement, but less pixels are available for usein calculation of TFLT. The larger the ADP is set, the less tear filmimage pixels that may be excluded in TFLT measurement, but it is morepossible that incorrect LLTs are included in the TFLT measurement. TheADP can be set to any value desired. Thus, the ADP acts effectively as afilter to filter out RGB values for tear film images that are deemed apoor match and those that may be ambiguous according to the ADP setting.This filtering can be included in the post-processing system 262 in FIG.28, as an example, and in step 346 therein, as an example.

TFT/Blink Stabilization

A contact lens wearing patient's tear film being stable or unstablebetween eye blinks can be another tear film characteristic that may beimportant in determining contact lens intolerance of the patient. Forexample, regions of the patient's tear film may have high peak LLTsduring the course of an interblink, but it may be desired to know ifthese LLTs are present during short or longer periods of time on apatient's tear film during blinks. In other words, it may be desired toknow how stable or unstable a patient's tear film is over an interblinkperiod. In this regard, FIG. 39 is an exemplary tear film stabilizationgraph 1100 that can be processed by the computer control system 240,using the contact lens-based region of interest 127 in FIG. 13 forexample, and displayed on the display of the OSI device 170 in FIG. 16to represent a contact lens wearing patient's tear film thicknessstabilization between eye blinks. In this regard, the graph 1100contains two axis. The X-axis is time. The Y-axis is thicknessmeasurements in micrometers (μm). A series of tear film stability images1102A-1102E are shown, with represent tear film stability of thepatient's tear film between blinks 1104A-1104D, which are represented byareas of void where no tear film stability information is present. Eachtear film stability image 1102A-1102E contains a lipid layer portion1106 and aqueous portion 1108 representing LLT and ALT of the patient'stear film over time between blinks, respectively. As illustrated in thelegend below tear film stability image 1102D, the blink portion 1104 isa period of time in which tear film information is not present, due toblink removal. The unstable portion 1110 of the tear film stabilityimage 1102D is the period of time between blinks where the LLT and ALTof the patient's tear film is changing significantly and thus isunstable. The stable portion 1112 of the tear film stability image 1102Dis the period of time between blinks where the LLT and ALT of thepatient's tear film is not changing significantly and thus is stable.

FIG. 40 is a flowchart illustrating an exemplary process for determininga movement of a patient's tear film following eye blinks indicative of acontact lens wearer patient's tear film thickness stabilizationfollowing eye blink in this example by analyzing the isolatedcontact-lens based region of interest and processing same using a lipidlayer-contact lens layer interference model (e.g., see FIGS. 6 and 127in FIG. 13). In this regard, the computer control system 240 in the OSIdevice 170 in FIG. 16 detects an initial frame captured by the videocamera 198 of the patient's tear film following a detected eye blink(block 1120). The computer control system 240 saves the initial frame asframe N (block 1122). The computer control system 240 then subtracts theaverage LLT and ALT between the current frame N and a subsequent framein a series of captured images of the patient's tear film (block 1124).This difference in average LLT and ALT in the consecutive images is thencompared to a predefined stablization value. The computer control system240 determines if the difference in average LLT and ALT in theconsecutive images is greater than the predefined stablization value fora defined number of consecutive frames (block 1126). If not, thecomputer control system 240 processes the next image in the series ofcaptured images of the patient's tear film before the next blink (blocks1128-1126). If the computer control system 240 determines the differencein average LLT and ALT in the consecutive images is greater than thepredefined stabilization value for a defined number of consecutiveframes in block 1126, the computer control system 240 sets thestabilization time of the patient's tear film as the difference betweenthe average LLT and ALT between images in which the difference inaverage LLT and ALT in consecutive images is greater than the predefinedstabilization value (block 1130), and the process ends (block 1132).These stabilization times can be used as stabilization values to berepresented in the tear film stabilization graph 1100 in FIG. 40.

Velocity Vector Map

It may also be desired provide a method for a technician to determinethe direction of movement of a patient's tear film between eye blinks asanother method to determine characteristics of the patient's tear film.The movement of tear film may help characterize the speed, break up, ordisappearance of tear film, and the spread, coverage and consistency ofTFLT within an area of interest. Understanding the direction of movementof the tear film, including the lipid layer, may assist in understandinghow the tear film is distributed across the patient's eye. In thisregard, a velocity vector image representing interference interactionsof specularly reflected light from a patient's tear film, such as image1032 in FIG. 41, can be provided, but with additional velocity vectorinformation 1142 superimposed on the image. The velocity vectors showthe direction and magnitude of velocity of the patient's tear film overa defined period of time, such as between eye blinks. The length of thevelocity vector represents magnitude of velocity. The direction of thevelocity vector represents the direction of movement of the patient'stear film over the defined period of time. In other words, the velocityvector information provides a “wind map” of the patient's tear film thatcan be used to visualize direction and amplitude of movement of thepatient's tear film.

Meniscus Height

Other methods may be employed to determine tear film characteristics ofa contact lens wearer patient's tear film. Tear film on top of thecontact lens 84 can also be analyzed but of particular interest is thetear film build-up on the edge of the contact lens 84. Due to wettingproperties and surface tension of tear film, a build-up or meniscus 1150(shown in FIG. 42) of tear film on the peripheral edge of the contactlens 84 is present. Evaluating the depth, slope, and amount of tear filmat this edge surface on the eye surface immediately adjacent the contactlens 84 can provide an indication of tear film quality and quantitythroughout the eye and under the contact lens 84. This area of interestbecomes a unique measurement, since the tear film will have a non-planarshape at the edge of the contact lens 84. The density of lipids at thislocation will indicate how well lubricated with lipids the tear film isand the surface of the eye 11 is directly adjacent to the contact lens84. These values—thickness, slope, density—can be a predictor of contactlens intolerance.

In this regard, the OSI device 170 in FIG. 16 could also be used tomeasure the height and/or slop of the meniscus of a patient's eye 11 tobe used to approximate the ALT of the patient's tear film. For example,FIG. 42 illustrates a side view of a patient's eye 11 in FIGS. 1-3described above. Common element numbers are shown to include commonfeatures. The meniscus 1150 of the eye 11 is shown therein. The videocamera 198 of the OSI device 170 in FIG. 16 could be used to image themeniscus 1150. The interference interactions of specularly reflectedlight from the meniscus 1150 may be correlated to a tear volume, whichmay be correlated to an ALT of the aqueous layer 14 of the patient'stear film.

In the process described above in FIG. 6 and discussed thereafter, thecontact lens-based region of interest of an image of a contact lenswearing patient's tear film was analyzed to determine tear filmcharacteristics indicative of contact lens intolerance. Because thecontact lens-based region of interest was analyzed, a lipidlayer-contact lens layer interference model was used in examplesdiscussed above since the lipid layer of the patient's tear film wasdisposed on top of a contact lens, which was thus modeled with its indexof refraction as an aqueous layer in the interference model. However,such is not limiting. It may also be desired to analyze the patient'stear film in non-contact lens-based regions of interest to determinetear film characteristics of the patient's tear film during contact lenswear. For example, areas at the interface of the contact lens may be ofinterest. Further, the patient's tear film could be analyzed innon-contact lens-based regions of interest during contact lens wear andthen in the entire regions of interest, including where the contact lenswas disposed on the cornea, after the contact lens is removed todetermine the difference in tear film characteristics as a result ofcontact wear and no contact wear.

In this regard, FIG. 43 is a flowchart of an exemplary process fordetermining tear film characteristics of a patient's ocular tear filmbased on analysis of imaged optical wave interference of specularlyreflected light from a non-contact lens-based region of interest of thepatient's tear film during contact lens wear, to determine the patient'sintolerance to contact lens wear. After the ocular tear film is imagedby the imaging device 40 in the OSI device 30 in FIG. 4A14, the computercontrol system 240 can isolate a non-contact lens-based region ofinterest in the first image or resulting image of a contact lens wearingpatient's tear film where the contact lens is not present (block 550 inFIG. 43). For example, the computer control system 240 may determine theedge of the contact lens 84 on the ocular tear film to determine thenon-contact lens-based regions of interest in the captured image of theocular tear film (block 552) and isolate the contact lens-based regionof interest from the image to be processed (block 554). The edge of thecontact lens 84 may be determined, for example, by a user indicating onthe GUI 280 of the OSI device 30, where the contact lens appears in thecaptured image of the patient's tear film during contact wear. Or, thecomputer control system 240 may analyze the pixels of a capturedimage(s) from the patient's ocular tear film to find a circular edgepattern therein to determine the location of the contact lens in thecapture image.

With continuing reference to FIG. 43, the computer control system 240can then process the non-contact lens-based region of interest accordingto any of the processing techniques described above to then convert thenon-contact lens-based region of interest to at least one color-basedvalue (block 556). The color-based value can then be compared to a tearfilm interference model that is not altered based on the index ofrefraction of a contact lens, as described above (block 558). Thecomputer control system 240 can then determine a tear filmcharacteristic above the non-contact lens-based region of interest ofthe patient's tear film based on a comparison of the color-based valueto the tear film interference model (block 560). As additional optionalsteps, the patient could be asked to remove their contact lens andanother image of the patient's tear film be captured, wherein thedifference between the tear film characteristics between the samenon-contact lens-based regions of interest in images with contact lenspresent due to contact lens wear and without a contact lens wearpresent, be determined (block 562), and a result generated based on thedifference for analysis (block 564).

As discussed above, there is a theoretical wavelength that will resultfrom constructive and destructive interference of reflected light fromthe tear film of a mammalian eye at the point of capture in an imagingdevice. The theoretical wavelength is based upon factors such as theindex of refraction of the lipid layer and the index of refraction ofthe aqueous layer for a tear film interference model, or a contact lensfor a lipid layer-contact lens layer interference model. As a result,there should be theoretical and predictable wavelengths that can then berepresented as RGB values in the computer control system. Therefore, theRGB values can be correlated to tear film measurements. However, theremay be factors that can cause the theoretical wavelength RGB values todeviate slightly without necessarily invalidating the above describedtear film measurement approach, but it might be able to be improvedupon. Thus, it may be desirable to provide an optical phantom to mimicor substantially mimic an ocular tear film for calibration purposes. Forexample, the optical phantoms of the present disclosure are constructedsuch that light rays emitted from a light source are specularlyreflected from the optical phantoms and undergo constructive anddestructive optical wave interference interactions that mimic orsubstantially mimic characteristics of light specularly reflected fromocular tear films. Ideal optical phantoms should be optically equivalentto a biological tear film. The optical phantoms should include twolayers, one layer with an index of refraction equal to that of meibomianlipid (1.4770 at 589 nm) on top of a substrate having an index ofrefraction equal to that of an aqueous layer (1.33698 at 589 nm)

However, attempts to find optical materials with indices of refractionidentical to the biological indices have been difficult. No exactmatches for the two refractive indices were found. Fortunately, apreviously unknown and breakthrough discovery made by the inventors ofthe present application was that if an optical phantom were manufacturedwith materials that include the same or substantially the same ratio ofindices of refraction as an ocular tear film, the phantom would mimic orsubstantially mimic the specularly reflective characteristics of anocular tear film. The materials provided in one example include acoating of magnesium oxide (MgO), which has a refractive index of 1.68at 589 nm, atop a preferred substrate of silicon optical crown glass,which has a refractive index of 1.517 at 589 nm. The ratio of theindices of refraction is 1.107 for the phantom materials is extremelyclose to 1.105, which is the ratio between the lipid and aqueousrefractive indices.

Using an optical phantom with the same or substantially the same ratioof indices as the lipid and aqueous layers will produce a color palettewith the same or substantially the same hue as the biological model, butwith a different lightness and chroma. The difference in lightness iscaused by a difference in reflection intensity of white light at theair/lipid/aqueous boundary versus the air/optical film/substrate coatingboundary. This is easily compensated for by using a neutral densityfilter 629 (shown in FIG. 44) in the imaging path of the imaging device194 to reduce the lightness of the incident light. The difference inchroma results from the interference between the recombination ofreflected and refracted rays of different magnitudes compared to thebiological model. This effect is compensated after the data is acquired.

Even though the thickness of optical coating which provides reflectedlight of a given hue will be different than the corresponding thicknessof meibum that produces light of the same or substantially the same hue,this effect can be readily compensated for by normalizing the lightnessand chroma based on the calculated differences between the biologicalmodel and the optical phantom. The optical path length is the same orsubstantially the same for both the phantom and the biological model toensure that the phase shift is identical and light is modulatedproportionately.

The reflected (double pass) optical path length is equal to:

$\Gamma = {2\; {nt}*{\cos ( {\sin^{- 1}( \frac{\sin ( \theta_{i} )}{n} )} )}}$

Where Γ is the optical path length, n is the index of refraction of themedium, t is the physical thickness of the medium, and θ_(i) is theangle of incidence. This assumes the angle of incidence, as measuredfrom the surface normal, is in a medium with index of refraction equalto one.

FIG. 44 is a block diagram of the OSI device 170 in FIG. 14, butadditionally configured to calibrate the OSI device to make accuratetear film measurements. FIG. 45 is a flowchart of an exemplary procedurefor calibrating the OSI device to make tear film measurements. Theprocedure begins by providing a wedge shaped optical phantom 642 havingan optical property that mimics or substantially mimics a predeterminedtear film thickness (block 662). Next, the wedge shaped optical phantom642 is placed within the imaging path of the imaging device 194 (block664). Then the illuminator 173 (i.e., a light source) is energized toilluminate the wedge shaped optical phantom 642 (block 666). Once thewedge shaped optical phantom 642 is illuminated, the imaging device 194is commanded via the illuminator driver and controller 628 to capture atleast one image of the wedge shaped optical phantom 642 (block 668). Theat least one image is then processed by the computer/computer controlsystem 240 to measure the optical property that mimics or substantiallymimics the predetermined tear film thickness (block 670). After adesired number of images of the wedge shaped optical phantom 642 istaken, another wedge shaped optical phantom 642 having a different thinfilm material thickness may be placed in the imaging path of the imagingdevice 194, and the steps of blocks 664 through 670 are repeated.

Selecting Thicknesses of Optical Phantom Coating

FIG. 46 is an exemplary RGB plot of an exemplary theoretical lipid colorpalette with points selected for phantoms. The palette is plotted for alipid layer thickness ranging from 10 to 300 nm, for the illuminator 173and the imaging device 194. The solid curving line shows the colorpalette predicted by a theoretical analysis given the measured opticalparameters of the imaging device 194 and the illuminator 173 and usingthe lipid and aqueous optical parameters from literature. Thecross-markers indicate the targeted LLT points on the palette for whichcorresponding phantoms were fabricated. These targeted LLT points areselected to encompass the full range of the palette and to quantify themajor inflection points along the solid curving line representing thetheoretical lipid color palette. The lipid layer thicknesses of theselected points are shown in the table of FIG. 47, along with theircorresponding optical pathlengths and phantom thicknesses.

FIG. 48 is a diagram that illustrates exemplary wedge phantomellipsometry measurement points. In particular, the graph depictsmagnesium oxide (MgO) thickness in nm versus x-coordinates andy-coordinates of the wedge shaped phantom front surface 644 coated withMgO. An ellipsometry analysis by an independent third-party providesconfirmation of the thickness of the MgO coating for each opticalphantom fabricated as well as the index of refraction and dispersion ofthe MgO coating. Dispersion is the phenomenon in which the index ofrefraction of a material is dependent on the wavelength of light. Theellipsometry measurements determine the refractive index at variouswavelengths, thereby quantifying the dispersion. A measurement ofthickness and refractive index is typically taken at twenty individualpoints for each of the phantoms to be measured. Usually, sixteen (16)measurement points are within 2 mm of the center of the face and fourpoints offset 6 mm radially from center, with each point 90° apart. Themeasurement pattern shown in FIG. 48 is represented by sixteen (16)black dots arrayed in the center of the wedge phantom diagram and fourpoints radially offset from the center.

FIG. 49 is a table listing exemplary phantom lipid layer thicknesses fornine sample wedge shaped optical phantoms 642 measured using exemplaryellipsometry along with corresponding biological lipid layerthicknesses. All measurements are recorded in nm, and include expectedphantom thickness and optical path length. The thickness results wereaveraged for each wedge shaped optical phantom 642 to provide an averagephantom thickness for each wedge shaped optical phantom 642. All indexof refraction results were averaged to provide a global index ofrefraction for all the wedge shaped optical phantoms 642. Since theindex of refraction is dependent on the material used and the processingparameters, no significant variability is expected from wedge to wedge.The phantom thickness measurements are shown in the table of FIG. 49.These phantom thicknesses were then converted back to lipid thicknessesusing an optical path length method. The average measured index ofrefraction of the MgO layer was 1.711 for light of 589 nm wavelength,somewhat different than the expected value of 1.68 nm. Consistentmeasurement data for a phantom having a 52 nm MgO coating was notavailable due to physical limitations of ellipsometry when measuringrelatively thin layers. Another complication that limits measurementconsistency is variability in coating thickness over the front surface644 of the wedge shaped optical phantom 642. However, since othermeasured phantom thicknesses were similar to expected thickness forother phantoms, an expected value is assumed to be accurate for thewedge shaped optical phantom 642 having the 52 nm MgO coating.

FIG. 50 is a table that presents a comparison of expected exemplaryinterference colors from optical phantoms and a theoretical model. Usingthe measured thickness and index of refraction data, the color expectedto be returned by each of the phantoms when imaged by the OSI device wascalculated. Values for the colors calculated are shown in the table ofFIG. 50 using an 8-bit RGB format as well as a hue, chroma, andlightness format. The RGB values assume that the intensity of theincident light has been reduced to 55 percent of the intensity output bythe illuminator under normal operation using the neutral density filter629 (as shown in FIG. 44). The intensity adjustment was made to avoidsaturation with the phantoms, since the amount of light returned fromthe phantoms is significantly higher in intensity than from a biologicalmodel. The intensity of the incident light does not affect hue. Anintensity effect on chroma and lightness is accounted for in subsequentanalysis.

Colorimetric Analysis of Optical Phantom Measurements Recorded Using anOSI System

One phantom of each thickness is placed in the imaging path of theimaging device 194 of the OSI device 170 (FIG. 44). A video is recordedfor each phantom thickness and exported from the OSI device 170 in amultimedia container format such as an audio video interleave (avi)format. The videos are then imported into a numerical computingenvironment such as Matlab®, which is executed by the OSI device toperform frame subtraction and erode/dilate algorithms. A frame isisolated from each video and a region of interest is selected for eachframe. A region of interest is located near the center of an illuminatortile to avoid any edge non-uniformity, and an attempt should be made toavoid any blemishes in the phantom coating. The average RGB values arethen determined within the region of interest for a phantom of eachthickness. A full color palette may then be created from 10 nm to 240 nmin 2 nm increments by fitting a cubic spline to the nine calculatedlipid color values. FIG. 51 is a graph that compares an original lipidcolor palette with a new exemplary lipid color palette based on thephantom measurements listed in the table of FIG. 50.

The performances of the original exemplary palette and the new palettecalculated from the optical phantoms were compared by analyzingsixty-one (61) videos captured using an OSI device like the OSI device170. One frame was selected from each video and analyzed using both thetheoretical palette and the phantom-derived palette. A conformancefactor that is the ratio of pixels that were matched to the palette andthe average distance between a matched pixel and the palette werecomputed for each of the frames using a software utility that includes amatching algorithm. The maximum acceptable distance between a pixel andthe nearest location on the palette that was considered a match was 30(in 8-bit RGB color space) for all points along both palettes. For thetheoretical palette, the average conformance factor for the sixty-one(61) frames was 0.916, while the average distance to the palette was15.05. For the phantom-derived palette, the average conformance factorwas 0.995 while the average distance to the palette was 10.63. Usingeither metric, the phantom-derived palette demonstrated a relativelylarge improvement over the theoretical palette.

A set of optical phantoms using a convex lens substrate was made at thesame time as the wedge shaped optical phantoms 642. A quality controlprocedure has been added to the OSI assembly process, wherein videos ofconvex shaped optical phantoms 652 having different thin film materialthicknesses are captured. These videos are analyzed using the OSI device170 to compare the captured images to the results obtained from thewedge shaped optical phantoms 642. The measured thickness is required tomatch the expected thickness to within 10 nm. This check ensures thatboth the optical and software systems of each OSI device 170 areoperating correctly in conjunction with one another prior to shipment tocustomers. This test also conclusively demonstrates that theinterferometric measurements provided by the OSI device 170 correlate toactual biological tear film thickness.

Although by example only a two wave model for an optical phantom such asthe wedge shaped optical phantom 642 is described above, it should beunderstood that the optical phantoms of the present disclosure may beextended to a three wave model by adding another material layer. Theadded material layer for the three wave model would mimic orsubstantially mimic the lipid layer and aqueous layer interface.

Because the embodiments disclosed herein involve use of a lipidlayer-contact lens layer interference model, it may be desired to employthe calibration techniques described above with regard to opticalphantoms to calibrate a tear film interference model into a lipidlayer-contact lens layer interference model instead of relying on atheoretical lipid layer-contact lens layer interference model. In thisregard, FIG. 52 is a flowchart of an exemplary process for determining alipid-layer-contact lens layer optical wave interference model based oncalibrating a tear film optical wave interference model. The process isbased on imaging a contact lens disposed on an optical phantom with theOSI device in FIG. 44 and analyzing the optical wave interference in thespecularly reflected light returned from the contact lens disposed onthe optical phantom. This also allows the lipid layer-contact lens layeroptical wave interference model to be based specifically on the exactcontact lens worn by the patient.

In this regard, as illustrated in FIG. 52, the contact lens 84 that isworn by the patient is disposed on an optical phantom 642 (block 566),as shown in FIG. 53. The contact lens 84 may be rinsed to remove alllipids that may be present from previous wear by a patient prior todisposing on the optical phantom 642. FIG. 53 references elements in theOSI device 170 and calibration system in FIG. 44, previously describedabove. With the contact lens 84 disposed on the optical phantom 642 andin the optical path of the illuminator 173 of the OSI device 170, thecontact lens 84 is illuminated by light 625 (see FIG. 44) (block 568 inFIG. 52). An image is obtained of the contact lens 84 and opticalphantom 642 with no lipids present, which will produce a certainbrightness due to the index or refraction and thickness of the contactlens 84 and optical phantom 642. The computer control system 240 canthen generate a lipid layer-contact lens layer interference model basedon the returned specularly reflected light versus what was expected forthe tear film interference model. These differences can be used togenerate the lipid-layer-contact lens layer interference by makingchanges to the index or refraction used for the aqueous layer in a tearfilm interference model (e.g., in the tear film interference modeldescribed above) that was calibrated based on the optical phantom 642without the contact lens 84 disposed thereon, to adjust the color scaletherein (block 569). Alternatively, each different contact lens 84 andvariation may be stored in the OSI device 170, which can be selected ifworn by a patient to generate the lipid layer-contact lens layerinterference model to be used by the OSI device 170.

Other processes for determining tear film characteristics of a contactlens wearing patient's tear film can be provided that do not requirecolor-based analysis. For example, FIG. 54 is a flowchart of anexemplary process for determining tear film characteristics of apatient's ocular tear film based on analysis of a non-contact lens-basedregion of interest of an image of a patient's tear film during contactlens wear, to determine the patient's intolerance to contact lens wear.In this regard, in a first step, the patient's ocular tear film having acontact lens 84 disposed on the patient's eye is performed by the OSIdevice 30 in FIG. 14 (block 570). The imaging device in the OSI device340 captures in at least one first image of the ocular tear film withthe contact lens 84 disposed thereon, optical wave interference ofspecularly reflected light from the ocular tear film, when the oculartear film is illuminated by the illuminator 36 (block 572). The computercontrol system 240 then isolates at least one non-contact lens-basedregion of interest in the at least one first image where the contactlens 84 is not present on the ocular tear film (block 574). As examples,as described above, the computer control system 240 may use edgeanalysis to determine the edge of the contact lens 84 in the at leastone first image (block 576) and isolate a defined area from the edge ofthe contact lens 84 where the contact lens 84 is not present on theocular tear film in the at least one image (block 578). For example,with a contact lens 84 in place, a tear film build up on the surface ofthe schlera or eye surface immediately adjacent to the contact lens 84may occur and be detectable in the captured image of the tear film. Thecomputer control system 240 can then determine a non-contact lens-basedtear film characteristic in the at least one non-contact lens-basedregion of interest of the at least one first image (block 580). Notethat the tear film characteristic does not have to be limited toobtaining a color-based value of the tear film in the captured image.

With continuing reference to FIG. 54, additional optical steps can beperformed. In this regard, the patient may be instructed to remove thecontact lens 84 from their eye to obtain an image of the ocular tearfilm without the contact lens 84 for comparison purposes. In thisregard, the computer controls system 240 causes the illuminator 173 inthe OSI device 170 to illuminate the ocular tear film of the patientwithout the contact lens 84 disposed on the patient's eye (block 582).The imaging device 40 captures in at least one second image of theocular tear film without the contact lens 84, optical wave interferenceof specularly reflected light from the ocular tear film, when the oculartear film is illuminated (block 584). The computer control system 240then determines a second non-contact lens-based tear film characteristicin at least one non-contact lens-based region of interest of the atleast one second image (block 586). The computer control system 240 thencan compare the first non-contact lens-based tear film characteristicbased on the contact lens 84 disposed on the ocular tear film to thesecond non-contact lens-based tear film characteristic based on thecontact lens 84 not being disposed on the ocular tear film (block 588).The computer control system 240 can then generate a resultingdifferential tear film characteristic based on the comparison of thefirst non-contact lens-based tear film characteristic based on thecontact lens 84 disposed on the ocular tear film to the secondnon-contact lens-based tear film characteristic based on the contactlens 84 not being disposed on the ocular tear film (block 590).

Further, a contact lens wearing patient's tear film without a contactlens described above can be analyzed immediately after the imaging ofthe patient's tear film with the contact lens disposed on the eye, orafter a period of time, for example 1 to 8 hours later. The imaging ofthe patient's tear film with and/or without contact lens wear can beperformed over a period of time with blinking involved, where theblinking images can be removed if desired, as discussed above. Thepatient may be informed to conduct a series of forceful blinks tostabilize the tear film before imaging of the tear film is performedand/or wear the contact lens in the office for a prescribed period oftime before imaging occurs. This amount of time can be as short as 2minutes and as long as 30 minutes as non-limiting examples. The OSIdevice can be used to determine the change in tear film characteristicsduring the session and over time, with and without contact lens wear todetermine the patient's tolerance or intolerance to contact lens wear assuch pertains to tear film.

Tear film characteristics of a contact lens wearing patient can bestored and sorted in a database, when desired, in the OSI device 30 overa period of times and analysis sessions to determine the change in tearfilm characteristics and for further analysis. Changes may occur due toincreased contact lens wear or reduced contact lens wear, as examples.

Many modifications and other embodiments of the disclosure set forthherein will come to mind to one skilled in the art to which thedisclosure pertains having the benefit of the teachings presented in theforegoing descriptions and the associated drawings. These modificationsinclude, but are not limited to, the type of light source orilluminator, the number of tiling groups and modes, the arrangement oftile groups, the type of imaging device, image device settings, therelationship between the illuminator and an imaging device, the controlsystem, the type of tear film interference model, and the type ofelectronics or software employed therein, the display, the data storageassociated with the OSI device for storing information, which may alsobe stored separately in a local or remotely located remote server ordatabase from the OSI device, any input or output devices, settings,including pre-processing and post-processing settings, materialsselected for phantoms, etc. Note that subtracting the second image fromthe first image as disclosed herein includes combining the first andsecond images, wherein like signals present in the first and secondimages are cancelled when combined. Further, the present disclosure isnot limited to illumination of any particular area on the patient's tearfilm or use of any particular color value representation scheme.

Therefore, it is to be understood that the disclosure is not to belimited to the specific embodiments disclosed and that modifications andother embodiments are intended to be included within the scope of theappended claims. It is intended that the present disclosure cover themodifications and variations of this disclosure provided they comewithin the scope of the appended claims and their equivalents. Althoughspecific terms are employed herein, they are used in a generic anddescriptive sense only and not for purposes of limitation.

We claim:
 1. A method for diagnosing contact lens intolerance on anocular tear film of a patient, comprising: illuminating the ocular tearfilm of the patient with a contact lens disposed on a patient's eye witha light source; capturing in at least one first image of the ocular tearfilm without the contact lens disposed on the patient's eye, opticalwave interference of specularly reflected light from the ocular tearfilm, when the ocular tear film is illuminated with the light source;isolating at least one contact lens-based region of interest in the atleast one first image where the contact lens is present on the oculartear film; converting the at least one contact lens-based region ofinterest in the at least one first image into at least one contactlens-based color-based value; comparing the at least one contactlens-based color-based value to a lipid layer-contact lens layer opticalwave interference model; and determining a contact lens-based tear filmcharacteristic of the at least one contact lens-based region of interestof the ocular tear film based on the comparison of the at least onecontact lens-based color-based value to the lipid layer-contact lenslayer optical wave interference model.
 2. The method of claim 1, furthercomprising: isolating at least one non-contact lens-based region ofinterest in the at least one first image where the contact lens is notpresent on the ocular tear film; converting the at least one non-contactlens-based region of interest in the at least one first image into atleast one non-contact lens-based color-based value; comparing the atleast one non-contact lens-based color-based value to a tear film layeroptical wave interference model; and determining a non-contactlens-based tear film characteristic of the at least one non-contactlens-based region of interest in the at least one first image based onthe comparison of the at least one non-contact lens-based color-basedvalue to the tear film layer optical wave interference model.
 3. Themethod of claim 2, further comprising: determining a difference betweenthe contact lens-based tear film characteristic to the non-contactlens-based tear film characteristic; and generating a resultingdifferential tear film characteristic based on the determined differencebetween the contact lens-based tear film characteristic to thenon-contact lens-based tear film characteristic.
 4. The method of claim2, wherein isolating the at least one non-contact lens-based region ofinterest in the at least one first image where the contact lens is notpresent comprises: determining an edge of the contact lens in the atleast one first image; and isolating a defined area from the edge of thecontact lens where the contact lens is not present on the ocular tearfilm in the at least one first image.
 5. The method of claim 4, whereindetermining the contact lens-based tear film characteristic comprisesdetermining a slope of a meniscus of the ocular tear film in the atleast one contact lens-based region of interest of the ocular tear filmbased on the comparison of the at least one contact lens-basedcolor-based value to the lipid layer-contact lens layer optical waveinterference model.
 6. The method of claim 1, wherein determining thecontact lens-based tear film characteristic comprises measuring a tearfilm layer thickness in the at least one contact lens-based region ofinterest in the at least one first image based on the comparison of theat least one contact lens-based color-based value to the lipidlayer-contact lens layer optical wave interference model.
 7. The methodof claim 1, wherein determining the contact lens-based tear filmcharacteristic comprises determining a viscosity of the ocular tear filmin the at least one contact lens-based region of interest in the atleast one first image based on the comparison of the at least onecontact lens-based color-based value to the lipid layer-contact lenslayer optical wave interference model.
 8. The method of claim 1, furthercomprising determining the contact lens-based tear film characteristiccomprises determining a movement rate of the ocular tear film in the atleast one contact lens-based region of interest in the at least onefirst image based on the comparison of the at least one contactlens-based color-based value to the lipid layer-contact lens layeroptical wave interference model.
 9. The method of claim 1, furthercomprising determining the contact lens-based tear film characteristiccomprises determining at least one of a size, a shape, a breakup, abreak up time, or a disappearance of the ocular tear film in the atleast one contact lens-based region of interest in the at least onefirst image based on the comparison of the at least one contactlens-based color-based value to the lipid layer-contact lens layeroptical wave interference model.
 10. The method of claim 1, furthercomprising: determining a type of contact lens disposed on the patient'seye; and generating the lipid layer-contact lens layer optical waveinterference model based on the determined type of contact lens.
 11. Themethod of claim 10, further comprising: disposing the contact lens on anoptical phantom comprised of at least one material layer disposed on asubstrate, and having a refractive index ratio between the at least onematerial layer and the substrate to mimic or substantially mimic arefractive index ratio between a lipid layer and an aqueous layer of anocular tear film; illuminating the contact lens disposed on the opticalphantom with the light source; and generating the lipid layer-contactlens layer optical wave interference model based on calibrating a tearfilm optical wave interface model generated from a phantom image of theoptical phantom without the contact lens disposed thereon.
 12. Themethod of claim 1, further comprising capturing a background signal fromthe ocular tear film with the contact lens disposed on the patient's eyein at least one background image; and wherein isolating the at least onecontact lens-based region of interest in the at least one first imagewhere the contact lens is present on the ocular tear film furthercomprises: subtracting the at least one background image from the atleast one first image to generate at least one resulting imagecontaining the optical wave interference of specularly reflected lightfrom the ocular tear film with the background signal removed or reduced;and isolating the at least one contact lens-based region of interest inthe at least one resulting image where the contact lens is present onthe ocular tear film.
 13. The method of claim 12, comprising capturingthe at least one background image when the light source is notilluminating the ocular tear film.
 14. The method of claim 12,comprising capturing the at least one background image when the lightsource is illuminating the ocular tear film.
 15. The method of claim 12,wherein capturing the background signal from the ocular tear film in atleast one background image further comprises not capturing specularlyreflected light from the ocular tear film.
 16. The method of claim 1,wherein the light source is comprised of a multi-wavelength Lambertianlight source.
 17. The method of claim 1, wherein the light source iscomprised of a mono-chromatic light source.
 18. The method of claim 1,further comprising displaying the at least one first image on a visualdisplay.
 19. The method of claim 1, further comprising displaying the atleast one contact lens-based region of interest in the at least onefirst image where the contact lens is present on the ocular tear film ona visual display.
 20. The method of claim 2, further comprisingdisplaying the at least one non-contact lens-based region of interest inthe at least one first image where the contact lens is present on theocular tear film on a visual display.
 21. An apparatus for diagnosingcontact lens intolerance on an ocular tear film of a patient,comprising: a light source configured to illuminate the ocular tear filmof a patient without a contact lens disposed on a patient's eye; animaging device configured to capture in at least one first image of theocular tear film without the contact lens disposed on the patient's eye,optical wave interference of specularly reflected light from the oculartear film, when the ocular tear film is illuminated with the lightsource; and a computer control system configured to: isolate at leastone contact lens-based region of interest in the at least one firstimage where the contact lens is present on the ocular tear film; convertthe at least one contact lens-based region of interest in the at leastone first image into at least one contact lens-based color-based value;compare the at least one contact lens-based color-based value to a lipidlayer-contact lens layer optical wave interference model; and determinea contact lens-based tear film characteristic of the at least onecontact lens-based region of interest of the ocular tear film based onthe comparison of the at least one contact lens-based color-based valueto the lipid layer-contact lens layer optical wave interference model.22. The apparatus of claim 21, wherein the computer control system isfurther configured to: isolate at least one non-contact lens-basedregion of interest in the at least one first image where the contactlens is not present on the ocular tear film; convert the at least onenon-contact lens-based region of interest in the at least one firstimage into at least one first non-contact lens-based color-based value;compare the at least one first non-contact lens-based color-based valueto a tear film layer optical wave interference model; and measure anon-contact lens-based tear film characteristic of the at least onenon-contact lens-based region of interest in the at least one firstimage based on the comparison of the at least one first non-contactlens-based color-based value to the tear film layer optical waveinterference model.
 23. A method for diagnosing contact lens intolerancein a patient, comprising: illuminating an ocular tear film of a patienthaving a contact lens disposed on a patient's eye with a light source;capturing in at least one first image of the ocular tear film with thecontact lens disposed on the patient's eye, optical wave interference ofspecularly reflected light from the ocular tear film, when the oculartear film is illuminated; isolating at least one non-contact lens-basedregion of interest in the at least one first image where the contactlens is not present on the ocular tear film; and determining anon-contact lens-based tear film characteristic in the at least onenon-contact lens-based region of interest of the at least one firstimage.
 24. The method of claim 23, wherein isolating the at least onenon-contact lens-based region of interest comprises: determining an edgeof the contact lens in the at least one first image; and isolating adefined area from the edge of the contact lens where the contact lens isnot present on the ocular tear film in the at least one first image. 25.The method of claim 24, wherein determining the non-contact lens-basedtear film characteristic comprises determining a slope of a meniscus ofthe ocular tear film in the at least one contact lens-based region ofinterest of the ocular tear film.
 26. The method of claim 23, whereindetermining the non-contact lens-based tear film characteristiccomprises: converting the at least one non-contact lens-based region ofinterest in the at least one first image into at least one firstnon-contact lens-based color-based value; and comparing the at least onefirst non-contact lens-based color-based value to a tear film layeroptical wave interference model.
 27. The method of claim 26, furthercomprising determining at least one of a size, a shape, a breakup, abreak up time, or a disappearance of the ocular tear film in the atleast one non-contact lens-based region of interest in the at least onefirst image based on the comparison of the at least one firstnon-contact lens-based color-based value to the tear film layer opticalwave interference model.
 28. The method of claim 26, further comprisingmeasuring a tear film layer thickness (TFLT) of the at least onenon-contact lens-based region of interest in the at least one firstimage based on the comparison of the at least one first non-contactlens-based color-based value to the tear film layer optical waveinterference model.
 29. The method of claim 26, further comprisingdetermining a viscosity of the ocular tear film in the at least onenon-contact lens-based region of interest in the at least one firstimage based on the comparison of the at least one first non-contactlens-based color-based value to the tear film layer optical waveinterference model.
 30. The method of claim 26, further comprisingdetermining a movement rate of the ocular tear film in the at least onenon-contact lens-based region of interest in the at least one firstimage based on the comparison of the at least one first non-contactlens-based color-based value to the tear film layer optical waveinterference model.
 31. The method of claim 23, further comprising:illuminating the ocular tear film of the patient without the contactlens disposed on the patient's eye; capturing in at least one secondimage of the ocular tear film without the contact lens disposed on thepatient's eye, optical wave interference of specularly reflected lightfrom the ocular tear film, when the ocular tear film is illuminated; anddetermining a second non-contact lens-based tear film characteristic inat least one non-contact lens-based region of interest of the at leastone second image.
 32. The method of claim 31, further comprisingcomparing the non-contact lens-based tear film characteristic based onthe contact lens disposed on the patient's eye to the second non-contactlens-based tear film characteristic based on the contact lens not beingdisposed on the patient's eye.
 33. The method of claim 32, furthercomprising generating a resulting differential tear film characteristicbased on the comparison of the non-contact lens-based tear filmcharacteristic based on the contact lens disposed on the patient's eyeto the second non-contact lens-based tear film characteristic based onthe contact lens not being disposed on the patient's eye.
 34. The methodof claim 32, wherein comparing the non-contact lens-based tear filmcharacteristic to the second non-contact lens-based tear filmcharacteristic comprising subtracting the non-contact lens-based tearfilm characteristic from the second non-contact lens-based tear filmcharacteristic
 35. The method of claim 31, wherein: determining thenon-contact lens-based tear film characteristic comprises: convertingthe at least one non-contact lens-based region of interest in the atleast one first image into at least one first non-contact lens-basedcolor-based value; and comparing the at least one first non-contactlens-based color-based value to a tear film layer optical waveinterference model; and determining the second non-contact lens-basedtear film characteristic comprises: converting the at least onenon-contact lens-based region of interest in the at least one secondimage into at least one second non-contact lens-based color-based value;and comparing the at least one second non-contact lens-based color-basedvalue to the tear film layer optical wave interference model.
 36. Themethod of claim 35, further comprising: measuring a tear film layerthickness (TFLT) of the at least one non-contact lens-based region ofinterest in the at least one first image based on the comparison of theat least one first non-contact lens-based color-based value to the tearfilm layer optical wave interference model; and measuring the TFLT ofthe at least one non-contact lens-based region of interest in the atleast one second image based on the comparison of the at least onesecond non-contact lens-based color-based value to the tear film layeroptical wave interference model.
 37. The method of claim 35, furthercomprising: determining a viscosity of the ocular tear film in the atleast one non-contact lens-based region of interest in the at least onefirst image based on the comparison of the at least one firstnon-contact lens-based color-based value to the tear film layer opticalwave interference model; and determining a viscosity of the ocular tearfilm in the at least one non-contact lens-based region of interest inthe at least one second image based on the comparison of the at leastone second non-contact lens-based color-based value to the tear filmlayer optical wave interference model.
 38. The method of claim 35,further comprising: determining a movement rate of the ocular tear filmin the at least one non-contact lens-based region of interest in the atleast one first image based on the comparison of the at least one firstnon-contact lens-based color-based value to the tear film layer opticalwave interference model; and determining a movement rate of the oculartear film in the at least one non-contact lens-based region of interestin the at least one second image based on the comparison of the at leastone second non-contact lens-based color-based value to the tear filmlayer optical wave interference model.
 39. The method of claim 23,further comprising capturing a background signal from the ocular tearfilm with the contact lens disposed on the patient's eye in at least onebackground image; and wherein isolating the at least one non-contactlens-based region of interest in the at least one first image where thecontact lens is present on the ocular tear film further comprises:subtracting the at least one background image from the at least onefirst image to generate at least one resulting image containing theoptical wave interference of specularly reflected light from the oculartear film with the background signal removed or reduced; and isolatingthe at least one non-contact lens-based region of interest in the atleast one resulting image where the contact lens is present on theocular tear film.
 40. The method of claim 39, comprising capturing theat least one background image when a light source is illuminating theocular tear film.
 41. The method of claim 39, wherein capturing thebackground signal from the ocular tear film in at least one backgroundimage further comprises not capturing specularly reflected light fromthe ocular tear film.
 42. The method of claim 31, further comprisingcapturing a second background signal from the ocular tear film withoutthe contact lens disposed on the patient's eye in at least one secondbackground image; and wherein isolating the at least one non-contactlens-based region of interest in the at least one second image withoutthe contact lens present on the ocular tear film further comprises:subtracting the at least one second background image from the at leastone second image to generate at least one second resulting imagecontaining the optical wave interference of specularly reflected lightfrom the ocular tear film with a background signal removed or reduced;and isolating the at least one non-contact lens-based region of interestin the at least one second resulting image without the contact lenspresent on the ocular tear film.
 43. The method of claim 23, wherein thelight source is comprised of a multi-wavelength Lambertian light source.44. The method of claim 23, wherein the light source is comprised of amono-chromatic light source.
 45. The method of claim 23, furthercomprising displaying the at least one first image on a visual display.46. The method of claim 31, further comprising displaying the at leastone second image on a visual display.
 47. The method of claim 23,further comprising displaying the at least one non-contact lens-basedregion of interest in the at least one first image where the contactlens is present on the ocular tear film on a visual display.
 48. Themethod of claim 31, further comprising displaying the at least onenon-contact lens-based region of interest in the at least one secondimage without the contact lens present on the ocular tear film on avisual display.
 49. An apparatus for diagnosing contact lens intolerancein a patient, comprising: an illuminator configured to illuminate anocular tear film of a patient having a contact lens disposed on apatient's eye; an imaging device configured to capture in at least onefirst image of the ocular tear film with the contact lens disposed onthe patient's eye, optical wave interference of specularly reflectedlight from the ocular tear film, when the ocular tear film isilluminated; a computer control system configured to: isolate at leastone non-contact lens-based region of interest in the at least one firstimage where the contact lens is not present on the ocular tear film; anddetermine a non-contact lens-based tear film characteristic in the atleast one non-contact lens-based region of interest of the at least onefirst image.
 50. The apparatus of claim 49, wherein: the illuminator isfurther configured to illuminate the ocular tear film of the patientwithout the contact lens disposed on the patient's eye; the imagingdevice is further configured to capture in at least one second image ofthe ocular tear film without the contact lens disposed on the patient'seye, optical wave interference of specularly reflected light from theocular tear film, when the ocular tear film is illuminated; and thecomputer control system is further configured to determine a secondnon-contact lens-based tear film characteristic in at least onenon-contact lens-based region of interest of the at least one secondimage.